CN1985854A - Plant lactobacillus composition and its application in strengthening intestinal immunobarrier - Google Patents
Plant lactobacillus composition and its application in strengthening intestinal immunobarrier Download PDFInfo
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Abstract
The present invention relates to a kind of composition containing plant lactobacillus LP-Onlly strain and its application in strengthening intestinal immunobarrier. The composition of the present invention can intervene the homing of intestinal lymphocyte, control the number of intestinal tract secretive IgA and intestinal lymphocyte, lower the endotoxin level, improve intestinal tract immunobarrier and prevent damage of intestinal tract immunobarrier caused by hunger, malnutrition, infection, etc, and prevent and treat intestinal inflammation, infectious diseases and immune disorder diseases.
Description
Technical field
The present invention relates to a kind of compositions and application in strengthening intestinal immunological barrier thereof that contains Lactobacillus, Lactobacillus plantarum kind, lactobacillus plantarum strain LP-Onlly.
Background technology
Intestinal is not only and is digested and assimilated and the important place of synthetic nutrient substance, also is the immune organ of human body maximum.70% human immunity tissue is present in intestinal, constitute (the Gut-AssociatedLymphoid Tissue of gut associated lymphoid tissue, GALT), contained lymphocyte quantity is higher than other lymphoid tissue far away, therefore, intestinal immunological barrier is to resisting antibacterial, virus, antigen and endotoxic invasion and attack, keeping that the aspects such as generation of stablizing, prevent inflammation of environment play important effect in the intestinal immune.And the to be intestinal mucosa immune important immunity of intestinal lymphocyte homing is one of movable, and participates in having constituted intestinal immunological barrier, and the balance of intestinal immunological barrier is had theory significance and clinical value.
Adhesion molecule MAdCAM-1 is the main addressin of intestinal lymphocyte homing, and (Immunoglobulin Super Family IgSF), has and the similar architectural feature of immunoglobulin (Ig) contactin.Under the normal condition, the MAdCAM-1 selective expression plays an important role to the directional migration of intestinal and the maintenance of intestinal immunological barrier to lymphocyte in the endotheliocyte of intestinal mucosa lamina propria and Peyer Patches endothelial venule (HEV).But under some pathological state, as clinically common have hunger, malnutrition, long-term total parenteral nutrition, infection, stress, the generation of diseases such as damage, immunologic derangement etc., gut barrier function damages, and certainly will influence the expression and the lymphocytic normal function of intestinal lymphocyte homing, immunoglobulin.
Discover that when hungry, the body protein level descends, lymphocyte quantity reduces, immunoglobulin level reduces, even influences the immunologic function of intestinal and whole body.Malnutrition can cause that gut-associated lymphoid tissue (GALT) produces the expression that the Th22 cytokine descends, reduces the CD11/CD18 adhesion molecule, influences the intestinal immunological barrier function.Long-term fasting or long-term total parenteral nutrition can cause the intestinal mucosa atrophy, and intestinal mucosa epithelium permeability strengthens, and intestinal incretion immunoglobulin A (SIgA) content descends, the intestinal immunological barrier dysfunction; According to reports, accept the total parenteral nutrition rat, intestinal intraepithelial lymphocytes, lamina propria lymphocyte quantity reduce, Peyer Patches atrophy, and CD4/CD8 ratio and enteral IgA level descend, and adhesion molecule MAdCAM-1 expresses reduction, and the GALT cell quantity reduces.Discover that the interactively of the infringement of gut barrier function and endotoxin and inflammatory mediator is very close during infection.It is the important pathological phenomenon of obstructive jaundice that intestinal bacterial translocation infects, and enteral lamina propria CD4+T cell, CD8+T cell and the adhesion molecule MAdCAM-1 of obstructive jaundice model mouse all reduce, and the intestinal immunological barrier function is destroyed.People such as Mao Yilei (Mao Yilei, Du Shunda, Ma Enling etc., the variation of rat gastrointestinal tract postoperative gut-associated lymphoid tissue and benefit are given birth to the effect of body, China's general surgery magazine, 2002,17 (10): 581-584) use gastrointestinal surgery model mouse research gut-associated lymphoid tissue and change the back discovery, the quantity that antibiotic has obviously reduced Peyer ' s Patches medium-sized lymphocyte sum and B cell is used in operation and operation back, prompting operation or antibiotic obvious damage gut-associated lymphoid tissue's function.
In recent years; along with to the intestinal immunological barrier function hunger, malnutrition, long-term total parenteral nutrition, infection, stress, the understanding of disease prognosis importance such as damage; people find that gradually enteral nutrition passes through the local nutrition of intestinal mucosa epithelial cell, stimulation; promote growth, the reparation of enterocyte; help to keep the integrity of intestinal mucosa epithelial cell 26S Proteasome Structure and Function; the protection gut barrier comprises the immunologic barrier function, prevents and/or treats the generation of enteritis, infectious disease and immunologic derangement disease.But common enteral nutrition preparation still can not be corrected the intestinal immunological barrier function effectively.
The invention describes the application of a new bacterial strain LP-Onlly (CGMCC NO.1258,16S rRNA gene GeneBank (NCBI) sequence accession number is AY590777) in strengthening intestinal immunological barrier of Lactobacillus plantarum (Lactobacillus plantarum).The invention still further relates to the combination of plant lactobacillus LP-Onlly and enteral nutrient composition, go back to the nest by intervening IL, intestinal secretion IgA and intestinal lymphocyte quantity, reduce level of endotoxin, improve intestinal immunological barrier, strengthen gut barrier function, ward off starvation, malnutrition, long-term total parenteral nutrition, infection, stress, the caused intestinal immunological barriers of disease such as damage, immunologic derangement destroy, and prevent and/or treat the generation of enteritis, infectious disease and immunologic derangement disease.
Summary of the invention
The purpose of this invention is to provide a kind of compositions that contains plant lactobacillus LP-Onlly;
The invention still further relates to described compositions and the enteral nutrient composition that contains plant lactobacillus LP-Onlly and be combined in the application that strengthens in the intestinal immunological barrier, can be used for hunger, malnutrition, long-term total parenteral nutrition, infection, stress, the caused intestinal immunological barriers of disease such as damage, immunologic derangement destroy, and prevent and/or treat the generation of enteritis, infectious disease and immunologic derangement disease.
The solution that realizes the foregoing invention purpose is:
A kind of plant lactobacillus LP-Onlly, CGMCC NO.1258.
Plant lactobacillus LP-Onlly, its 16S rRNA gene GeneBank (NCBI) sequence accession number is AY590777.
The application of plant lactobacillus LP-Onlly in strengthening intestinal immunological barrier.
Plant lactobacillus LP-Onlly and enteral nutrient composition are combined in the application that strengthens in the intestinal immunological barrier.
The combination of plant lactobacillus LP-Onlly and enteral nutrient composition, can be used for warding off starvation, malnutrition, long-term total parenteral nutrition, infection, stress, the caused intestinal immunological barriers of disease such as damage, immunologic derangement destroy.
Plant lactobacillus LP-Onlly and enteral nutrient composition combination can be used for preventing and/or treating the generation of enteritis, infectious disease and immunologic derangement disease.
Description of drawings
Fig. 1: terminal ileum mucosa-immune group CD4 picture
Fig. 2: terminal ileum mucosa-immune group CD8 picture
Fig. 3: terminal ileum mucosa-immune group MAdCAM-1 picture
Fig. 4: terminal ileum mucosa-immune group IgA picture
Fig. 5: Peyer Patches SABC CD4 picture
Fig. 6: Peyer Patches SABC CD8 picture
Fig. 7: Peyer Patches SABC MAdCAM-1 picture
Fig. 8: Peyer Patches SABC IgA picture
The specific embodiment
Plant lactobacillus LP-Onlly of the present invention directly separates acquisition in healthy babies feces, its form is shaft-like, and Gram-positive does not form spore, produces lactic acid, amphimicrobian.It can utilize L-arabinose, sorbitol, 6-(.alpha.-D-galactosido)-D-glucose., D-turanose, D-arabitol, gluconic acid sodium salt, Alpha-Methyl-D-mannoside, can not utilize sorbose, rhamnose, D-Tagatose, Alpha-Methyl-D-glycoside.
This plant lactobacillus LP-Onlly in December in 2004 6 days at China Committee for Culture Collection of Microorganisms common micro-organisms center (address: No. 13, one of Zhong Guan-cun, Haidian District, BeiJing, China city, Institute of Microorganism, Academia Sinica) preservation, and receive preservation registration number CGMCC NO.1258.
The plant lactobacillus LP-Onlly that the present invention relates to, its 16S rna gene sequence is put on record in GeneBank (NCBI), and its accession number is AY590777.
The plant lactobacillus LP-Onlly compositions that the present invention relates to and the combination of enteral nutrient composition can independent assembly packagings or hybrid packed.The carrier of the plant lactobacillus LP-Onlly that relates to can be the culture medium of this strain fermentation, and especially based on bean sprout, Fructus Setariae Germinatus etc., suitable culture medium can also contain water soluble dietary fiber, oligosaccharide etc.Plant lactobacillus LP-Onlly carrier according to the present invention mainly contains Lactobacillus plantarum viable bacteria and metabolite as being oral liquid, and its number of viable reaches 1.0 * 10
6～2.0 * 10
8CFU/ml; As be solid dosage formss such as granule, tablet or capsule, then its number of viable reaches 1.0 * 10
8～2.0 * 10
10CFU/g.The enteral nutrition that relates to can be conventional enteral nutrient composition, also can contain the specific nutrient with certain pharmacotoxicological effect especially, as glutamine, arginine, omega-fatty acid, taurine, antioxidant, protein oligopeptide etc.
The plant lactobacillus LP-Onlly compositions that the present invention relates to and the combination of enteral nutrient composition, administration in any suitable manner, preferred oral administration or rectally, as Orally taken product can be oral liquid, granule, tablet or capsule, also can make the enema dosage form, can also insert intestinal or directly insert intestinal canal administration through stomach by conduit.
Further specify the present invention below in conjunction with embodiment and Tu.
Embodiment 1: zoopery
1. severe acute pancreatitis in rats (Severe Acute Pancreatitis, SAP) foundation of model
The present invention adopts male SD rat, body weight 250～300g (Medical Center of Fudan University's animal center provides), water 12h is can't help in fasting, after 20g/L ketalar (100mg/kg body weight) the intraperitoneal injection anesthesia, rat is fixed in dorsal position, cervical region and abdominal part unhairing, the sterilization of 1g/L benzalkonium bromide tincture, shop aseptic towel.Median incision is opened the abdominal cavity; the pancreas and the bile duct that find lamellar to distribute in the duodenum inboard; No. 4.5 syringe needles are driven in the wrong direction through mesentery offside intestinal wall insert bile duct; ligation bile duct end and syringe needle; noinvasive vascular clamp folder closes hepatic portal place bile duct, evenly slowly injects 50g/L sodium taurocholate (1ml/kg), about 5min of the time of injecting; unclamp vascular clamp and ligature behind the 10min, intestinal wall place point of puncture sewed up in 8 words.
Pocket is imbedded another silica gel tube at the about 40cm small intestinal of distance caecum place, and external diameter is 12mm, and it is drawn between nape portion omoplate along subcutaneous the moving under water of stomach wall, gives intestinal nutrient solution and plant lactobacillus LP-Onlly through this pipe.Paramedian incision is cut off skin of neck, and passivity is isolated external jugular vein, inserts the silica gel tube that external diameter is 12mm through external jugular vein, and hypodermic tunnel moves under water and draws to nape portion, gives parenteral nutrition liquid through this pipe.External jugular vein intubate and jejunum fistulation pipe pass the spiral spring circle and are connected with 360 ° of rotary infusion sets.Parenteral nutrition liquid and intestinal nutrient solution are evenly imported with microinfusion pump 24h.
2. plant lactobacillus LP-Onlly fermentation liquid, parenteral nutrition (PN liquid), enteral nutrition (EN liquid) are formed
The plant lactobacillus LP-Onlly fermentation liquid that adopts among the present invention is that starting strain fermentation bean sprout produces " ANGLI No. 1 oral liquid " with the plant lactobacillus LP-Onlly, contains active plant lactobacillus LP-Onlly in the product, and number of viable reaches 1.0 * 10
6～2.0 * 10
8CFU/ml, this product is sold by Only Co., Ltd., Shanghai Jiantong Univ..
PN liquid is conventional parenteral nutrition composition, is made up of glucose, aminoacid, lipomul, vitamin, mineral etc.
EN liquid is formed through the warm water dilution by the Ensure Powder that Dutch NUTRICIA Nutricia (Zoetermeer) company produces, and Ensure Powder is made up of maltodextrin, dextrose syrup, lactalbumin hydrolysate, vegetable oil, medium chain triglyceride, vitamin, minerals etc.
3. zoopery grouping
The laboratory animal of modeling success is divided into three groups at random, preceding 24h all gives normal saline 2ml/h:(1) parenteral nutrition group (PN group), gave PN on the 2nd～6 day and support that microinfusion pump keeps the about 33ml/h of transfusion speed, average every rat transfusion quantity about 80ml/ days; (2) parenteral nutrition+enteral nutrition group (PN+EN group) gave PN+EN on the 2nd～6 day and supports that wherein 80% hot nitrogen amount is provided by PN, average every the about 64ml/ of rat amount of infusion days; 20% is provided by EN, Ensure Powder with warm water by 1g: 4ml is diluted to 16ml, and the reuse normal saline is diluted to 24ml with the latter with 1: 2 (volume ratio), and 1ml/h splashes into through jejunum fistulation pipe, EN energy supply every day 200.6kj/kg (48kcal/kg).(3) parenteral nutrition+enteral nutrition+plant lactobacillus LP-Onlly fermentation liquid group (PN+EN+LP-Onlly group), giving PN+EN on the 2nd～6 day supports, PN liquid+EN liquid support amount is organized with PN+EN, divides through jejunum fistulation pipe simultaneously to splash into plant lactobacillus LP-Onlly fermentation liquid 10ml/d altogether for three times.Above-mentioned three groups of rats are observed rat ordinary circumstance, reaction sensitivity, mobility and death condition in modeling success back; All above-mentioned experimental group rats were all put to death in the 7th day and sampling detects or observes.
The normal control group gives the external jugular vein intubate equally, and fasting be can't help water 24h and put to death sampling detection or observation.
4. observation index
(1) the easy bit rate of flora
Get caval vein blood 1ml, pour in the heart and brain leachate pipe 35 ℃ behind mesentery lymphoid tissue, liver middle period, the lungs lobus dexter tissue homogenate respectively into and increase bacterium and cultivate, 18-24h is placed on the U.S. blue dull and stereotyped 35 ℃ of cultivations in Yihong, and counting is identified behind the 18-24h.The easy bit rate of flora=cultivate total sample number * 100% of male sample number/detection.
(2) terminal ileum mucosal immunity groupization and Peyer ' s knot MAdCAM-1, CD4, CD8, IgA analyze
All tissue specimens are fixed with 10% neutral buffered formalin; Adopt paraffin embedding, the thick serial section of 5 μ m drips antibody after, aquation cured through taking off and 0.01mol/L (PH6.0) the citrate buffer antigen retrieval.Use HPIAS1000 high-definition color picture and text pathological replacement analytical system, optical densitometric method is measured the corresponding cell CD4 in every visual field, CD8, MAdCAM-1, IgA density, and the positive colour developing of calculating area accounts for the percentage ratio in the measurement window.
5. interpretation of result
(1) each experimental group ordinary circumstance and death condition
All appearance is dispirited in various degree behind the experimental group rat modeling 24h, and the irritant reaction degree descends to external world, and is wherein obvious with the PN group.
PN+EN+LP-Onlly group mortality rate is starkly lower than PN group (P＜0.05), and the PN+EN group is compared difference not statistically significant (P＞0.05) with the PN group, but totally is better than PN group (5238%VS 7561%); The PN+EN group is compared difference not statistically significant (P＞0.05) with the PN+EN+LP-Onlly group.
Table 1 is respectively organized mortality rate %
| Group | The total routine number of modeling | Dead routine number | Mortality rate |
| PN group PN+EN group PN+EN+LP-Onlly group | 41 21 20 | 31 11 10 | 75.61％ 52.38％ △50.00％ △△ |
Compare with the PN group
△P=0.0641
△ △P=0.0455
Above results suggest, plant lactobacillus LP-Onlly and enteral nutrition combination help to improve the Severe Acute Pancreatitis SAP Rats survival rate.
(2) the easy bit rate of flora
PN+EN group, PN+EN+LP-Onlly group are lower than the PN group, and wherein the PN+EN+LP-Onlly group is minimum, and the PN+EN group is compared difference not statistically significant (P=0.6256) with the PN+EN+LP-Onlly group.
Table 2. is respectively organized the easy bit rate % of internal organs flora
| Group | The routine number of surviving | Sample number | Easy bit rate |
| PN group PN+EN group PN+EN+LP-Onlly group | 10 10 10 | 40 40 40 | 70.25％ 30.50％ △27.50％ △△ |
Compare with the PN group,
△P=0.0003,
△ △P=0.0001
Above results suggest, plant lactobacillus LP-Onlly and enteral nutrition combination help to reduce the easy bit rate of Severe Acute Pancreatitis SAP Rats Organs and Tissues flora.
(3) terminal ileum mucosal immunity groupization
Shown in Fig. 1～4 and table 3, model experiment group end ileal mucous membrane CD4, CD8, MAdCAM-1, IgA express and all are lower than normal control group (P＜0.05), show Severe Acute Pancreatitis SAP rat intestinal immunological barrier functional lesion, the modeling success.But the PN group is compared with PN+EN group, PN+EN+LP-Onlly group, and the former is starkly lower than two groups of backs, and significant difference (P＜0.05) is arranged; Then comparing difference not statistically significant (P＞0.05) between two groups is higher than the PN+EN group but add plant lactobacillus LP-Onlly group numerical value generally.Show that the Severe Acute Pancreatitis SAP rat gives parenteral nutrition+enteral nutrition and the simple parenteral nutrition group of parenteral nutrition+enteral nutrition+plant lactobacillus LP-Onlly helps to improve the intestinal immunological barrier function; This results suggest, plant lactobacillus LP-Onlly help to improve the ileal mucous membrane immunologic function.
Each group end ileal mucous membrane SABC of table 3. (%,
)
| Group | CD4 | CD8 | MadCAM-1 | IgA |
| PN group PN+EN group PN+EN+LP-Onlly group matched group | 2.98±0.59 △5.78±1.79 6.32±2.23 10.10±2.87 * | 2.93±0.45 △ 4.12±0.43 4.16±0.55 5.22±0.73 * | 2.96±0.59 △ 4.80±0.65 5.13±0.75 8.10±0.99 * | 8.63±2.01 △ 11.51±2.25 13.26±2.53 15.62±1.68 * |
△Compare P＜0.05 with all the other groups,
*Compare P＜0.05 with all the other groups
(4) Peyer Patches SABC:
Shown in Fig. 5～8 and table 4, CD4, CD8, MAdCAM-1, IgA express and all are lower than normal control group (P＜0.05) among the model experiment group Peyer Patches, show Severe Acute Pancreatitis SAP rat intestinal immunological barrier functional lesion, the modeling success.But the PN group is compared with PN+EN group, PN+EN+LP-Onlly group, and in CD4 and IgA expression, the former is starkly lower than two groups of backs, and significant difference (P＜0.05) is arranged; Then comparing difference not statistically significant (P＞0.05) between two groups is higher than the PN+EN group but add plant lactobacillus LP-Onlly group numerical value generally; And in CD8, MAdCAM-1 expressed, the PN group was lower than the PN+EN group, and significant difference (P＜0.05) is arranged, and added the plant lactobacillus LP-Onlly group and significantly was lower than PN+EN group (P＜0.05).Show that the Severe Acute Pancreatitis SAP rat gives the simple parenteral nutrition of enteral nutrition and helps to improve the intestinal immunological barrier function, plant lactobacillus LP-Onlly then helps to improve the expression of CD8 and adhesion molecule MAdCAM-1 among the Peyer Patches, this results suggest plant lactobacillus LP-Onlly can improve IL goes back to the nest, and strengthens the intestinal immunological barrier function.
Table 4. respectively organize Peyer Patches SABC (%,
)
| Group | CD4 | CD8 | MadCAM-1 | IgA |
| PN group PN+EN group PN+EN+LP-Onlly group matched group | 2.53±0.39 3.81±1.05 △ 4.38±1.12 △ 8.32±0.91 * | 2.72±0.32 3.15±0.45 △ 3.56±0.63 △# 5.01±0.53 * | 1.16±0.38 2.05±0.20 △2.51±0.32 △#3.03±0.52 * | 3.70±0.91 6.31±1.72 △6.99±1.22 △9.18±1.34 * |
△Compare P＜0.05 with the PN group,
#Compare P＜0.05 with the PN+EN group,
*Compare P＜0.05 with all the other groups
6. conclusion
The above results shows, plant lactobacillus LP-Onlly of the present invention helps to improve the expression of CD8 and adhesion molecule MAdCAM-1 among the Peyer Patches, and the prompting plant lactobacillus LP-Onlly can improve IL goes back to the nest, and strengthens the intestinal immunological barrier function.The expression that plant lactobacillus LP-Onlly and enteral nutrient composition combination will improve CD4, CD8, MAdCAM-1 and IgA among terminal ileum mucosa and the Peyer Patches strengthens the intestinal immunological barrier function.
Embodiment 2: plant lactobacillus LP-Onlly and enteral nutrition combination are to the influence of severe pancreatitis patients natural history
1. Severe Acute Pancreatitis SAP patient screening
Select 30 examples to meet the patient of acute critical pancreatitis diagnostic criteria.Male's 17 examples among the 30 routine patients, women's 13 examples; Age 20-87 year (average 59.9 ± 16.4 years old); Morbidity is to being admitted to hospital 25.6 ± 15.6 hours average times; 30 routine patients morbidity all has colic symptoms, heating (T＞38 ℃), and WBC raises (＞10
9/ L), blood/amylase in urine rising (blood amylase＞110U/L; Amylase in urine＞641U/L); The highest 6500U/L of blood amylase, average 1236 ± 1373U/L; The highest 20000U/L of amylase in urine, average 5636 ± 6439U/L.18 examples are with jaundice (total bilirubin＞18 μ mol/L) when being admitted to hospital; 13 examples are with abnormal liver function (ALT＞65U/L or AST＞37U/L); 6 examples are with renal dysfunction (BUN＞6.4mmol/L or Cr＞115 μ mol/L).30 examples are all taked expectant treatment.Allly need surgical intervention person, the overweight person of the state of an illness (APACHE II scoring＞25 minutes) has serious metabolic disease person (diabetes, hyperlipemia etc.), not at the row of this research.
2. plant lactobacillus LP-Onlly fermentation liquid, parenteral nutrition (PN liquid), enteral nutrition (EN liquid) are formed
The plant lactobacillus LP-Onlly fermentation liquid that adopts among the present invention is that starting strain fermentation bean sprout produces " ANGLI No. 1 oral liquid " with the plant lactobacillus LP-Onlly, contains active plant lactobacillus LP-Onlly in the product, and number of viable reaches 1.0 * 10
6～2.0 * 10
8CFU/ml, this product is produced by Only Co., Ltd., Shanghai Jiantong Univ..
PN liquid is conventional parenteral nutrition composition, is made up of glucose, aminoacid, lipomul, vitamin, mineral etc.
EN liquid adopts the Ensure Powder (Nutricia, 126g/ bag can be washed into the 500ml nutritional solution) of Dutch NUTRICIA Nutricia (Zoetermeer) company to be main energy sources.
3. experiment is divided into groups and Therapeutic Method
30 routine Severe Acute Pancreatitis SAPs are divided into three groups at random, i.e. conventional therapy group (conventional group), parenteral nutrition treatment group (PN group) and the outer and enteral nutrition treatment group (LP-Onlly group) of plant lactobacillus LP-Onlly associating intestinal.
(1) conventional therapy group
Adopt traditional fasting, gastrointestinal decompression, the conventional liq treatment, the full dose fluid infusion, about 3000ml/ days, based on 10%GS, 5%GS, part 5%GNS, balance liquid etc., press glucose in the fluid infusion: insulin adds insulin than about 6g: 1g.Electrolyte requirement NaCl 4.5g/ days, KCl 3g/ days.Vein uses Cefuroxime Sodium (6g/ days), metronidazole antibiotic such as (200ml/ days).Use human albumin to correct to the hypoproteinemia person, vein replenished 10-20g/ days.The primary growth chalone (Shi Taning or kind peaceful, 6mg/24h keeps) of being admitted to hospital suppresses the digestive gland secretion.Generally alleviate to patient's abdominal part sign, no abdominal distention is vomitted etc., can stop gastrointestinal decompression.Routine blood test, blood/amylase in urine is normal more than 3 days, can consider to open gradually diet.
(2) parenteral nutrition group (PN group)
PN is through the central vein infusion, 1 week of enforcement time.(Intralipid SSPC) provides energy, and heating load 25-30kcal/kg/ days, the glycolipid energy supply was than 1-2: 1 with 50% glucose and 20% lipomul; (Novamin SSPC) for nitrogen, is 0.12-0.15g/kg/ days for the nitrogen amount with 8.5% Novamin.Add simultaneously vitamin (Soluvit, SSPC), trace element (Anda U.S., SSPC) and K
+, Na
+In electrolyte; In glucose: the ratio of insulin is that 4-5g: 1g adds insulin, and all nutritional solutions are sneaked in three liters of bags, and the nutrient input angle of incidence is no less than 12-14h (the PN prescription sees Table 4).The same antibiotic such as Cefuroxime Sodium, metronidazole that use, somatostatin such as kind peaceful, Shi Taning, using method is not used preparations such as blood plasma or human albumin with conventional group.
(3) the outer and enteral nutrition group (LP-Onlly group) of plant lactobacillus LP-Onlly associating intestinal
1 week of enforcement time.The energy supply is organized with PN.EN begins the back to give Ensure Powder 126g/ days in 1-2 days, gave infusion velocity 120ml/h after 3 days Ensure Powder 252g/ days.The energy shortage part is replenished by PN, and the PN part is by 10%GS and 20% lipomul (Intralipid, SSPC) energy supply, (Novamin is SSPC) for nitrogen, through peripheral vein approach infusion for 8.5% Novamin, when single bottle of lipomul of infusion and Novamin, the about 120ml/h of control transfusion speed.Implement EN and merge use plant lactobacillus LP-Onlly (use amount: 50ml/ days, inject) simultaneously through jejunal nutrient canal.Anti-anaerobic agents such as metronidazole will not use, and Cefuroxime Sodium etc. are still normal to be used with conventional group, does not use preparations such as blood plasma or human albumin.
4. observation index
(1) blood/amylase in urine, routine blood test, hepatic and renal function
Venous blood collection, iodine colorimetry is surveyed blood/amylase in urine; Automatic Blood Cell Analyzer is measured routine blood test and hepatic and renal function.
(2) plasma endotoxin
Plasma endotoxin changed before and after endotoxin test kit (U.S. Accociates of Cape Cod LAL of company test kit) was surveyed treatment.
(3) complication
After the patient leaves hospital medical history data is put in order statistics, comprise complication, hospital stays, hospitalization cost.Complication comprises the local complication (pancreatic necrosis, pancreatic abscess, pancreas pseudocyst) of pancreas, whole body complication (septicemia, organ function depletion), PN complication (catheter infections, metabolism complication), EN complication (pipe obstruction, vomiting, diarrhoea).
5. interpretation of result
(1) blood/amylase in urine, routine blood test, hepatic and renal function
The equal no difference of science of statistics of These parameters (P＞0.05) (seeing table 5 and table 6 for details) between three groups.Change each index variation tendency unanimity in time.Blood/amylase in urine generally, WBC etc. are all on a declining curve and recover normal gradually.
Table 5. blood/amylase in urine
| Index | The 1st day | The 4th day | The 7th day |
| The conventional group of blood amylase (U/L) normal value (30-110) conventional group PN group LP-Onlly group amylase in urine (U/L) normal value (32-641) PN group LP-Onlly group | 968.1±300.3 1528.3±1801.1 1211.8±1603.3 8436.7±7361.0 4137.8±5612.0 4334.4±5901.6 | 178.1±120.1 183.4±116.6 125.3±64.5 1044.6±882.6 2754.9±6068.6 495.7±234.3 | 99.3±60.4 74.0±47.2 65.7±36.3 292.4±338.3 244.0±127.1 259.6±124.6 |
Table 6.WBC, hepatic and renal function
| Index | The 1st day | The 8th day |
| The conventional group of WBC (109/L) normal value (4-10) conventional group PN group LP-Onlly group ALT (U/L) normal value (0-65) conventional group PN group LP-Onlly group AST (U/L) normal value (8-37) conventional group PN group LP-Onlly group total bilirubin (μ mol/L) normal value (0-18) conventional group PN group LP-Onlly group BUN (mmol/L) normal value (2.5-6.4) conventional group PN group probiotic group Cr (μ mol/L) normal value (53-115) PN group LP-Onlly group | 17.0±5.5 14.6±3.7 14.3±2.7 112.2±148.4 135.4±183.2 29.0±15.5 94.0±107.7 97.5±132.4 40.2±34.8 25.2±19.6 40.3±49.7 22.8±7.0 5.8±1.9 5.7±3.5 4.2±0.9 78.2±25.6 92.6±27.8 73.6±18.1 | 10.7±3.9 11.6±6.6 9.2±3.1 29.1±15.4 35.5±33.0 25.7±16.6 28.9±15.9 29.8±9.6 25.1±6.7 15.1±6.0 16.8±13.5 14.9±5.9 6.5±7.2 3.5±1.0 4.4±1.3 83.7±69.9 79.7±32.1 62.9±19.1 |
(2) plasma endotoxin
Treatment first three groups plasma endotoxin meansigma methods no difference of science of statistics.Conventional group second all level of endotoxin are than raise in first week (p＜0.05); The PN group changes not obvious (p＞0.05); The LP-Onlly group then has remarkable reduction (p＜0.05).Level of endotoxin after relatively treating, the LP-Onlly group significantly is lower than conventional therapy group (p＜0.01), compares no difference of science of statistics (table 7) with the PN group.This results suggest, plant lactobacillus LP-Onlly are united outside the intestinal and enteral nutrition helps to reduce Severe Acute Pancreatitis SAP patient's level of endotoxin, strengthen intestinal barrier function.
Plasma endotoxin changes (Pg/ml) before and after table 7. treatment
| The 1st week | The 2nd week | |
| Conventional group PN group LP-Onlly group | 3.13±0.71 2.77±0.64 3.18±0.69 | 4.08±1.24 * 2.90±0.79 2.71±0.65 △# |
Annotate:
*Compare p＜0.05 with the 1st week,
#Compare p＜0.05 with the 1st week
△Compare p＜0.01 with the routine group
(3) complication
Conventional therapy group 1 routine patient is admitted to hospital and renal failure occurs, concurrent respiratory failure after 1 week.Dead after the 13rd day family members' abandoning cure of being admitted to hospital.All the other 29 routine patients all cure and leave hospital.The complication situation sees Table 8 in the statistics course of disease).As seen PN group and LP-Onlly group aspect severe complication (the local complication of pancreas, septicemia, organ failure) are less than conventional group.This results suggest, the outer and enteral nutrition of plant lactobacillus LP-Onlly associating intestinal helps to alleviate Severe Acute Pancreatitis SAP patient's complications, alleviates the state of an illness.
Table 8. complication situation
| Conventional group | The PN group | The LP-Onlly group | |
| Dead necrosis of pancreas abscess of pancreas pancreas false cyst septicemia Organ Failure: cardiovascular lung kidney | 1 3 0 1 0 0 3 1 | 0 2 0 0 0 0 0 0 | 0 0 0 0 0 0 0 0 |
| The vomiting and diarrhoea of liver brain stomach and intestine blood coagulation system catheter infections Metabolic complication pipe obstruction | 0 1 0 0 / / / / / | 0 0 0 0 0 0 / / / | 0 0 0 0 / / 0 0 5 |
(4) length of stay and hospitalization cost
Statistical analysis shows that total cost conventional therapy group is significantly higher than PN group and LP-Onlly group (p＜0.01), no difference of science of statistics (P＞0.05) between PN group and the LP-Onlly group.Length of stay LP-Onlly group was lower than conventional group 34.8 days in 20.9 days and PN organizes 24.2 days.This results suggest plant lactobacillus LP-Onlly associating enteral nutrition helps the Severe Acute Pancreatitis SAP patient to reduce complication, reduces medical expense and shortens the hospital stays.
Table 8. length of stay (my god) and expense (unit)
| Length of stay (my god) | Total cost (unit) | |
| Conventional group PN group LP-Onlly group | 34.8±17.4 24.2±12.8 20.9±8.9 | 49434.21±30796.07 19938.56±11389.27 ** 18529.83±15523.88 ** |
Annotate:
*Compare (p＜0.01) with the routine group
6. conclusion
Plant lactobacillus LP-Onlly associating enteral nutrition of the present invention helps to reduce absorption, the enhancing gut barrier function of intestinal endotoxin, reduces complication rate, reduces hospitalization cost, shortens length of stay.
Claims (10)
1. a compositions that contains Lactobacillus plantarum is characterized in that, described compositions comprises plant lactobacillus LP-Onlly and intestinal nutrient solution;
Plant lactobacillus LP-Onlly wherein, CGMCC NO.1258, its 16S rna gene sequence is put on record in Gene Bank (NCBI), and its accession number is AY590777;
Described intestinal nutrient solution is conventional enteral nutrient composition or the nutritional solution with pharmacotoxicological effect.
2. compositions according to claim 1 is characterized in that, also contains conventional parenteral nutrition composition in the described compositions.
3. compositions according to claim 1; it is characterized in that described nutritional solution with pharmacotoxicological effect is glutamine, arginine, omega-fatty acid, taurine, antioxidant, protein oligopeptide, maltodextrin, dextrose syrup, lactalbumin hydrolysate, vegetable oil, medium chain triglyceride, vitamin, mineral or trace element.
4. compositions according to claim 1 is characterized in that, the carrier of described plant lactobacillus LP-Onlly can be the culture medium of this strain fermentation.
5. compositions according to claim 4 is characterized in that described culture medium is based on bean sprout, Fructus Setariae Germinatus.
6. compositions according to claim 5 is characterized in that described culture medium also contains water soluble dietary fiber, oligosaccharide.
7. compositions according to claim 1 is characterized in that the carrier of described plant lactobacillus LP-Onlly is an oral liquid, and number of viable reaches 1.0 * 10
6～2.0 * 10
8CFU/ml.
8. compositions according to claim 1 is characterized in that the carrier of described plant lactobacillus LP-Onlly is a solid dosage forms, and number of viable reaches 1.0 * 10
8～2.0 * 10
10CFU/g.
9. according to the described arbitrary compositions of claim 1～8, it is characterized in that described compositions is an independent assembly packaging or hybrid packed.
10. the described compositions of claim 1 is applied to strengthen intestinal immunological barrier, prevents and/or treats enteritis and infectious disease.
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| CNA2006101477333A CN1985854A (en) | 2006-12-22 | 2006-12-22 | Plant lactobacillus composition and its application in strengthening intestinal immunobarrier |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006101477333A CN1985854A (en) | 2006-12-22 | 2006-12-22 | Plant lactobacillus composition and its application in strengthening intestinal immunobarrier |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102292431B (en) * | 2008-12-03 | 2014-02-19 | Cj第一制糖株式会社 | Novel lactobacillus plantarum and composition containing the same |
| CN103805547A (en) * | 2013-03-07 | 2014-05-21 | 练冬娣 | Lactobacillus plantarum LP-12 and application thereof in preparation of efficient animal intestinal canal modifier |
| CN104921107A (en) * | 2014-12-31 | 2015-09-23 | 广州宇晟生物科技有限公司 | Enteral nutrient and preparation method thereof |
| CN111035662A (en) * | 2019-11-19 | 2020-04-21 | 西南大学 | Application of lactobacillus plantarum S58 in preparation of products for relieving damage of spicy food to digestive system |
-
2006
- 2006-12-22 CN CNA2006101477333A patent/CN1985854A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102292431B (en) * | 2008-12-03 | 2014-02-19 | Cj第一制糖株式会社 | Novel lactobacillus plantarum and composition containing the same |
| CN103805547A (en) * | 2013-03-07 | 2014-05-21 | 练冬娣 | Lactobacillus plantarum LP-12 and application thereof in preparation of efficient animal intestinal canal modifier |
| CN103805547B (en) * | 2013-03-07 | 2016-02-17 | 练冬娣 | A kind of plant lactobacillus LP-12 and the application in the efficient animal intestinal conditioning agent of preparation thereof |
| CN104921107A (en) * | 2014-12-31 | 2015-09-23 | 广州宇晟生物科技有限公司 | Enteral nutrient and preparation method thereof |
| CN111035662A (en) * | 2019-11-19 | 2020-04-21 | 西南大学 | Application of lactobacillus plantarum S58 in preparation of products for relieving damage of spicy food to digestive system |
| CN111035662B (en) * | 2019-11-19 | 2023-03-07 | 西南大学 | Application of lactobacillus plantarum S58 in preparation of product for relieving damage of spicy food to digestive system |
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