CN111227243A - Food with special medical application formula - Google Patents

Food with special medical application formula Download PDF

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CN111227243A
CN111227243A CN202010129786.2A CN202010129786A CN111227243A CN 111227243 A CN111227243 A CN 111227243A CN 202010129786 A CN202010129786 A CN 202010129786A CN 111227243 A CN111227243 A CN 111227243A
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autophagy
food
hmb
special medical
sarcopenia
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翁敏
樊文星
杨柳青
杨亚男
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First Affiliated Hospital of Kunming Medical University
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    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00Drugs for disorders of the muscular or neuromuscular system
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs

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  • Urology & Nephrology (AREA)
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Abstract

The invention specifically relates to a formula food with special medical application, which comprises β -hydroxy- β -methylbutyric acid as an active ingredient and has a treatment effect on chronic renal failure sarcopenia, wherein β -hydroxy- β -methylbutyric acid regulates and controls the expression reversal of autophagy-related genes and autophagy key proteins to treat the chronic renal failure sarcopenia.

Description

Food with special medical application formula
Technical Field
The invention relates to the field of health-care food, in particular to food with a special medical application formula.
Background
Chronic renal insufficiency is a common and serious disease that endangers human health. With the worsening of Renal function, accumulation of metabolites, reduction of dietary intake, micro-inflammation, insulin resistance and the like, patients with Chronic Renal Failure are very likely to suffer from muscle mass reduction, muscle strength reduction, selective muscle structure change and obvious muscle atrophy, which is called Chronic Renal Failure Sarcopenia (CRF-S). The chronic renal failure sarcopenia is manifested by hypodynamia, difficulty in walking, falling down and even fracture, and meanwhile, the chronic renal failure sarcopenia can also increase cardiovascular complications, hospitalization rate, all-cause mortality and social and family economic burden of patients. However, it is easy to ignore because of its long course of disease and lack of specific expression. Therefore, improvement of chronic renal failure sarcopenia is a clinical problem to be solved.
The muscle mass of the aged with chronic obstructive pulmonary disease is reduced by 1.5g/d HMB, wherein the muscle mass of the aged with chronic obstructive pulmonary disease is reduced by 0.81kg, 0.77kg, 0.82kg and 0.65 kg respectively after 30 days, 60 days and 90 days, and the muscle mass of the aged with chronic obstructive pulmonary disease is reduced by more than 2.6g after oral administration, wherein the muscle mass of the aged with chronic obstructive pulmonary disease is reduced by more than 2.5 g/d HMB after 24 weeks, and the aged with chronic obstructive pulmonary disease is reduced by more than 2.6g after oral administration.
Disclosure of Invention
In order to solve the above problems, the present invention aims to provide a food with a formulation for specific medical use for the treatment of sarcopenia with chronic renal failure.
In order to achieve the purpose, the technical scheme of the invention is that the food with a formula for special medical purposes comprises β -hydroxy- β -methylbutyric acid as an active ingredient.
Furthermore, the formula food for special medical application has a treatment effect on chronic renal failure sarcopenia.
Furthermore, the β -hydroxy- β -methylbutyric acid regulates the expression of autophagy-related genes and autophagy key proteins and treats sarcopenia caused by chronic renal failure.
Further, the autophagy-related genes are LC3B, Beclin1, ULK1, Atg5, Atg7, Atg13 and vps-34.
Further, the β -hydroxy- β -methylbutyric acid can be used for reducing the expression of the autophagy related gene.
Further, the autophagy key protein is LC3B and p 62.
Further, the β -hydroxy- β -methylbutyric acid regulates the down-regulation of the expression of an autophagy key protein LC3B and the up-regulation of the expression of p 62.
Compared with the prior art, the invention has the beneficial effects that:
(1) β -hydroxy- β -methylbutyric acid (HMB) can effectively improve sarcopenia caused by chronic renal failure, and the weight, muscle mass and muscle cross-sectional area of a rat are increased by regulating autophagy key genes and proteins, so that the sarcopenia of the rat with the chronic renal failure is improved.
(2) The project is based on the research on the aspects of pathogenesis and intervention treatment of the common chronic renal failure sarcopenia which does not cause enough attention, provides a new thought and a new treatment target point for clinically treating the disease, and has good popularization and application prospects.
Detailed Description
The technical solution of the present invention will be further described with reference to the following specific examples.
As shown in figures 1-6, a food for special medical purposes, the active ingredient of the food for special medical purposes is β -hydroxy- β -methylbutyric acid.
Furthermore, the formula food for special medical application has a treatment effect on chronic renal failure sarcopenia.
Further, the β -hydroxy- β -methylbutyric acid regulates the expression of autophagy-related genes and autophagy key proteins to treat sarcopenia caused by chronic renal failure.
Further, the autophagy-related genes are LC3B, Beclin1, ULK1, Atg5, Atg7, Atg13 and vps-34.
Further, the β -hydroxy- β -methylbutyric acid is used for reducing the expression of the autophagy related gene.
Further, the autophagy key protein is LC3B and p 62.
Further, the β -hydroxy- β -methylbutyric acid regulates the down-regulation of the expression of an autophagy key protein LC3B and the up-regulation of the expression of p 62.
Experimental example: male SD rats 6-8 weeks old and weighing about 250-300 g were divided into model, control and HMB treated groups according to a randomized basis, each group consisting of 6 rats. Model group: administering 250mg/kg/d adenine continuously for 14 days, and then changing to alternate daily administration (adenine dose and concentration are unchanged) until 28 days; control group: infusing the stomach with normal saline with the same volume and frequency as those of the adenine for 28 days; HMB treatment group: the administration is carried out for 35 days from 7 days before the start of the adenine intragastric administration to the end of the adenine intragastric administration, and the administration is carried out for 320mg/kg/d HMB. Detecting the weight of each group of rats, right tibialis anterior muscle (wet weight, dry weight/weight and cross-sectional area), related blood indexes and pathological sections of kidney and gastrocnemius to confirm the success of model building of chronic renal failure sarcopenia rats and the treatment effect of HMB; the rat gastrocnemius autophagy key gene and protein are detected to prove that HMB improves chronic renal failure sarcopenia by regulating autophagy.
From the second week of the experiment, the weight, the wet weight, the dry weight/the weight and the cross-sectional area of the right tibialis anterior muscle of the model group are reduced compared with those of the control group, and the difference has statistical significance (P < 0.05); after 35 days of HMB treatment, the rat body weight, wet weight, dry weight/body weight and cross-sectional area of the tibialis anterior muscle were all increased compared to the model group with statistical differences (P <0.05) (see table 1, table 2 and fig. 1 and fig. 2).
TABLE 1 comparison of rat body weight, tibialis anterior wet weight, dry weight/body weight for control, model and HMB-treated groups
Figure BDA0002395482390000041
Figure BDA0002395482390000051
The difference between the model group and the control group has statistical significance, and P is less than 0.05; indicates that the difference between the HMB treated group and the model group was statistically significant, P < 0.05.
TABLE 2 comparison of the Cross-sectional areas of tibialis anterior muscles of rats in the control, model and HMB-treated groups
Figure BDA0002395482390000052
Figure BDA0002395482390000061
The difference between the model group and the control group has statistical significance, and P is less than 0.05; indicates that the difference between the HMB treated group and the model group was statistically significant, P < 0.05.
Compared with the control group, the blood of the model group rats has obviously increased creatinine, urea nitrogen, uric acid and phosphorus, and the difference has obvious statistical significance (P <0.001), while the concentration of hemoglobin and calcium is obviously reduced compared with the control group, and the difference has obvious statistical significance (P <0.001) (see table 3).
TABLE 3 comparison of blood indices (M + -Q) of rats in control group and model group
Figure BDA0002395482390000071
#The difference between the model group and the control group has significant statistical significance, P<0.001。
The pathological section (HE staining) of the detected rat kidney shows that the number of glomeruli of the rat kidney in the control group is normal, no fibrosis and pathological changes of crescent moon and the like are seen (see figure 3B), the renal tubular morphology is normal, and no granuloma, inflammatory cell infiltration and fibrosis are seen in renal interstitium (see figure 3A); the glomerulus of the rat in the model group has no obvious pathological change, but renal tubule atrophy and cyst cavity expansion exist, crystals are deposited in the tubule cavity, a small amount of granular casts and protein casts are visible in part of the renal tubule cavity, foreign body granuloma formation, inflammatory cell infiltration and fibrous tissue hyperplasia are visible in renal interstitium (see figures 3C and 3D).
The pathological section (HE staining) of the gastrocnemius of the rat is detected to show that the gastrocnemius cells of the rat in the control group have normal morphology, no nuclear increase, no fibrous tissue hyperplasia and no lipofuscin (figure 4A); the rat gastrocnemius fibrous tissue of the model group is hyperplastic, the muscle fiber is thin and disorganized (see fig. 4B); the rats treated with HMB had improved gastrocnemius muscle fiber proliferation and collagen fiber content compared to the model group (see FIG. 4C).
In conclusion, the model of the chronic renal failure sarcopenia rats can be successfully made, and the HMB can improve the chronic renal failure sarcopenia.
Further detecting mRNA expression amounts of rat gastrocnemius autophagy key genes LC3B, Beclin1, ULK1, Atg5, Atg7, Atg13 and vps-34 and levels of key proteins LC3B and p62 thereof, and researching whether HMB improves chronic renal failure sarcopenia by regulating autophagy.
Compared with the control group, the model group rat autophagy genes LC3B, Beclin1, ULK1, Atg5, Atg7, Atg13 and vps-34 are obviously up-regulated, and the difference has significant statistical significance (P <0.001) (see Table 4 and figure 5); the expression of autophagy key protein LC3B is up-regulated, the expression of P62 is down-regulated, and the difference is statistically significant (P <0.05) (see Table 5 and FIG. 6). The expression of the autophagy-related genes and proteins was reversed after HMB intervention treatment, with statistical differences ((P <0.001, P <0.05) (see table 5 and fig. 6).
TABLE 4 gastrocnemius autophagy group in control group, model group and HMB-treated groupComparison by LC3B, Beclin1, UlK1, Atg5, Atg7, Atg13 and vps-34
Figure BDA0002395482390000081
Figure BDA0002395482390000082
Figure BDA0002395482390000091
#The difference between the model group and the control group has significant statistical significance, P<0.001;##Shows that the difference of the HMB treatment group and the model group has significant statistical significance, P<0.001。
Table 5: comparison of gastrocnemius autophagy genes p62 and LC3B in control group, model group and HMB-treated group
Figure BDA0002395482390000092
The difference between the model group and the control group has statistical significance, and P is less than 0.05; indicates that the difference between the HMB treated group and the model group was statistically significant, P < 0.05.
In summary, chronic renal insufficiency leads to complex pathophysiological changes, in which decreased protein synthesis and increased degradation lead to loss of muscle mass, and ultimately to sarcopenia. In recent years, a great deal of foreign research shows that HMB plays an important role in the intervention treatment of sarcopenia caused by various diseases, and the supplement of HMB can be used for improving the sarcopenia. However, the therapeutic efficacy and molecular mechanism of HMB in sarcopenia with chronic renal failure is not clear. Our study showed that in rats with chronic renal failure and sarcopenia, the weight, the wet weight, the dry weight/the weight and the cross-sectional area of the tibialis anterior muscle of the rats are increased compared with those of the model group, namely, the sarcopenia is improved. The autophagy-related genes in the gastrocnemius of the rat in the model group are obviously up-regulated, the expression of autophagy key protein LC3B is up-regulated, and the expression of p62 is down-regulated. After HMB treatment, the expression of the above genes and proteins was reversed in rats. It was thus confirmed that HMB can improve chronic renal failure sarcopenia, and it is to improve chronic renal failure sarcopenia by modulating autophagy.
The above-mentioned embodiments are only examples of the present invention, which is only used for illustrating the present invention, and not for limiting the present invention, and any changes and substitutions that do not go through the inventive step should be covered within the protection scope of the present invention, and the protection scope of the present invention should be subject to the scope defined by the claims.
Drawings
FIG. 1: body weight (g) change in control, model and HMB treated rats from week 1 to week 5: the weight of the model group is reduced compared with that of the control group, and the difference has statistical significance (P < 0.05); the difference in weight gain from day 14 in the HMB treated group compared to the model group was statistically significant (. about.p < 0.05);
FIG. 2: comparison of wet weight, dry weight/body weight, cross-sectional area of the tibialis anterior muscle of rats in control group, model group and HMB treated group: compared with the control group, the model group has reduced muscle mass and cross-sectional area of the tibialis anterior muscle, and the difference has statistical significance (P < 0.05); the HMB treatment group has the indexes increased compared with the model group, and the difference has statistical significance (P < 0.05);
fig. 3 (confirmation of successful modeling of rat model of chronic renal failure): rat kidney pathological sections (HE staining) of control, model and HMB treated groups; wherein, A: control rats normal renal tubules (X100); b: normal kidney tissue (X100) of control rats; c: model group rat renal tubular atrophy + crystallization + foreign body giant cell (X200); d: HMB-treated rat kidney crystals (X200);
FIG. 4: pathological sections of gastrocnemius muscles of rats in a control group, a model group and an HMB-treated group (HE staining); wherein, A: control group (X100); b: a model group (X100); c: HMB treatment group (X100);
FIG. 5: the expression level of autophagy-related gene mRNA in gastrocnemius muscles of rats in the control group, the model group and the HMB-treated group was changed: the expression of the mRNA of the autophagy related gene of the rat in the model group is obviously increased compared with that of the control group, and the difference has obvious statistical significance (#P<0.001); rat autophagy-related gene in HMB treatment groupThe mRNA expression is obviously reduced compared with the model group, and the difference has statistical significance (##P<0.001)。
FIG. 6: changes in expression of autophagy key proteins LC3B and p62 in gastrocnemius muscles of rats in control, model and HMB treated groups: compared with the control group, the model group rats have higher autophagy key protein LC3B, lower P62 and statistical significance in difference (P < 0.05); HMB treated rats the autophagy key protein was reversed compared to the model group, and the differences were statistically significant (. about.p < 0.05).

Claims (5)

1. A food with a formula for special medical purposes is characterized in that the effective component of the food is β -Hydroxy- β -Methylbutyrate (β -Hydroxy- β -methylbutryrate, HMB).
2. The food formulation for special medical use according to claim 1, characterized in that: the special medical food has a treatment effect on chronic renal failure sarcopenia.
3. The food formulation for special medical use according to claim 2, characterized in that: the food with the special medical purpose formula regulates the expression of autophagy-related genes and autophagy key proteins, and improves the sarcopenia caused by chronic renal failure.
4. The food formulation for special medical use according to claim 3, characterized in that: downregulating the expression of autophagy-related genes LC3B, Beclin1, ULK1, Atg5, Atg7, Atg13, and vps-34.
5. The food formulation for special medical use according to claim 3, characterized in that: reversing autophagy key proteins LC3B, p 62.
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104411305A (en) * 2012-03-19 2015-03-11 雅培制药有限公司 Beta-hydroxy-beta-methylbutyric acid for improving glucose tolerance
CN107373673A (en) * 2017-08-22 2017-11-24 河北健素临床营养有限公司 Full nutrition formula food for the disability patient of disability caused by cardiovascular and cerebrovascular diseases half
CN109641135A (en) * 2016-01-21 2019-04-16 代谢科技有限公司 Beta-hydroxy-Beta-methyl butyric acid (HMB) is used to adjust the composition and method of autophagy and lipophagia

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104411305A (en) * 2012-03-19 2015-03-11 雅培制药有限公司 Beta-hydroxy-beta-methylbutyric acid for improving glucose tolerance
CN109641135A (en) * 2016-01-21 2019-04-16 代谢科技有限公司 Beta-hydroxy-Beta-methyl butyric acid (HMB) is used to adjust the composition and method of autophagy and lipophagia
CN107373673A (en) * 2017-08-22 2017-11-24 河北健素临床营养有限公司 Full nutrition formula food for the disability patient of disability caused by cardiovascular and cerebrovascular diseases half

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
刘佳配等: "自噬-溶酶体系统与慢性肾衰竭营养不良", 《临床医学工程》 *
刘佳配等: "自噬-溶酶体系统与慢性肾衰竭营养不良", 《临床医学工程》, no. 06, 15 June 2018 (2018-06-15), pages 835 - 836 *
朴英实等: "《分子病理生物学实验技术指南》", 知识产权出版社, pages: 87 - 88 *
邵枫等: "自噬在肾脏疾病发生中的作用", 《中华肾病研究电子杂志》, no. 05, 15 October 2014 (2014-10-15), pages 268 - 271 *

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Application publication date: 20200605