CN103520363A - Application of Xinnaoxin capsules in preparation of medicament for treating cerebral ischemia - Google Patents
Application of Xinnaoxin capsules in preparation of medicament for treating cerebral ischemia Download PDFInfo
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Abstract
The invention discloses application of Xinnaoxin capsules in preparation of a medicament for treating cerebral ischemia. Research results show that the Xinnaoxin capsules can increase the normal-pressure closed anoxic survival time of a mouse, and increase the decapitation gasping time to prompt that the Xinnaoxin capsules have a certain protective effect on the mouse in an anoxic environment. Besides, the Xinnaoxin capsules can obviously reduce the cerebral water content, cerebral indexes, cerebral capillary permeability and the like of a cerebral ischemia mouse caused by artery ligation of two side necks, and prompt that the Xinnaoxin capsules has a certain protective effect on experimental cerebral ischemia.
Description
Technical field
The invention belongs to field of medicaments, be specifically related to the application of XINNAOXIN JIAONANG in preparation treatment brain ischemia medicament.
Background technology
Ischemic cerebrovascular is a kind of commonly encountered diseases, frequently-occurring disease of serious harm human health, and its mortality rate is high.At present treatment ischemic cerebrovascular except rational diet, suitably take exercise, discontinue the habit of smoking and drinking, form good living habit; generally all to adopt clinical treatment; but there is the harm such as hemorrhage and reperfusion injury in treatment application; therefore inquire into the pathogenesis of ischemic brain injury, the medicine of exploitation protection ischemic brain injury has important theory significance and clinical value.
XINNAOXIN JIAONANG is S&P Pharmaceutical Co., Ltd.'s product, and the accurate word Z20025866 of traditional Chinese medicines, cures mainly supplementing QI and nourishing YIN, blood circulation promoting and blood stasis dispelling.But the effect at learning memory disorder have not been reported.
Summary of the invention
Goal of the invention: the object of the present invention is to provide the new application of XINNAOXIN JIAONANG.
Technical scheme: the invention discloses the application of XINNAOXIN JIAONANG in preparation treatment brain ischemia medicament.
Above-mentioned XINNAOXIN JIAONANG is the Radix Rhodiolae of 3～6 parts by parts by weight, the Fructus Lycii of 5～15 parts, and the Fructus Hippophae of 3～9 parts forms.
Beneficial effect: result of study shows, XINNAOXIN JIAONANG can increase mice atmospheric closed the survival time under hypoxic condition, and increases the broken end breathing time of dehiscing, and prompting XINNAOXIN JIAONANG has certain protective effect to anaerobic environment mice.In addition, XINNAOXIN JIAONANG can obviously reduce brain water content, cerebral index and the brain capillary permeability etc. of cerebral ischemia mice due to bilateral ligation, and prompting XINNAOXIN JIAONANG has certain protective role to experimental cerebral ischemia.
The specific embodiment
Embodiment 1:
The protective effect of XINNAOXIN JIAONANG to experimental cerebral ischemia mice
1 experiment material
1.1 medicine
XINNAOXIN JIAONANG, content is chocolate brown powder, 0.5g/ grain, lot number: 120803 S&P Pharmaceutical Co., Ltd.; During experiment, remove capsule shell, grind content, with distilled water, be configured to desired concn.Nimodipine, specification: 30mg, lot number: BJ09103, Bayer HealthCare Co; During experiment, be ground to powder, with distilled water, be configured to desired concn.Azovan blue, lot number: W20111101, Chemical Reagent Co., Ltd., Sinopharm Group.Methanamide, lot number: 11032310336, Nanjing Chemistry Reagent Co., Ltd..Coomassie brilliant blue, superoxide dismutase (SOD), malonaldehyde (MDA), acetylcholinesterase (AChE), nitric oxide (NO), nitric oxide synthetase (NOS), glutamic acid (Glu) test kit all build up biological company limited purchased from Nanjing.
1.2 instrument
Electronic balance (Beijing Sai Duolisi balance company limited); Thermostatic drying chamber (Ecocell, Germany); Microplate reader (Thermo, the U.S.); High speed centrifuge (Sigma, 1-15K), digital display thermostat water bath (HH-4, Changzhou Guohua Electric Appliance Co., Ltd.), XW-80A vortex mixer (Shanghai Hu Xi analytical tool factory); Micropipettor; Manual homogenizer; SMG-2 channel-type water maze (institute of Materia Medica,Chinese Academy of Medical Sciences); STT-2 diving tower instrument (institute of Materia Medica,Chinese Academy of Medical Sciences).
1.3 laboratory animal
Clean level ICR mice, 18～22g, male ，You Yangzhou University's comparative medicine center provides, laboratory animal production licence number: SCXK(Soviet Union) 2012-0004.Animal sub-cage rearing, keeps 12h circadian rhythm, and 22 ± 1 ℃ of room temperatures, freely drink water and ingest.
2 experimental techniques
The mensuration of 2.1 mice atmospheric closed the survival time under hypoxic conditions
50 of clean level ICR mices, are divided into 5 groups at random, i.e. blank group (gavage equal-volume normal saline), nimodipine group (40mg/kg/d), the basic, normal, high dosage group of XINNAOXIN JIAONANG (170mg/kg/d, 340mg/kg/d, 680mg/kg/d).Blank group and each administration group ig, 2 times/d, continuous 3d, 1h after last administration, puts into respectively by each group mice the airtight wide mouthed bottle that volume is 125ml immediately, in bottle, is placed with 10g sodica calx, observes and record the mouse survival time.
Dehisce after the 2.2 mices broken ends mensuration of breathing time
Grouping and administration same 2.1.1h after last gavage, breaks end in mouse ear bottom fast with shear, and record, from broken end to dehiscing for the last time the snorting time, is the breathing time of dehiscing.
The mensuration of 2.3 acute incomplete cerebral ischemic model mouse brain indexes, brain water content
90 of clean level ICR mices, are divided into 6 groups at random.Be sham operated rats, model group, nimodipine group, the basic, normal, high dosage group of XINNAOXIN JIAONANG.Dosage and mode are with 2.1, and successive administration 3d, after last administration 1h, with after 10% chloral hydrate (350mg/kg, ip) anesthesia, lies on the back mice to be fixed on operating-table, routine disinfection, neck median incision, separated bilateral common carotid arteries (CCA).Introduce two-wire ligation respectively, form acute experiment incomplete cerebral ischemic model; Only separated bilateral common carotid arteries but not ligation of sham operated rats.After 3h, broken end, opens cranium and gets brain fast, removes cerebellum and oblongata.Weigh (wet brain weight), calculate cerebral index (heavy * 100/ body weight of cerebral index=wet brain).Then in 110 ℃ of baking boxs, bake to constant weight, analytical balance is weighed (dry brain weight), calculates brain water content, the brain water content %=(brain weight-dry brain weight that wet)/brain weight * 100% wets.
The mensuration of 2.4 acute incomplete cerebral ischemic model mouse brain capillary permeabilities
Mice group, administration and modeling are with 2.3.Model group and each administration group be 5min tail vein injection 0.5% Evans blue 50mg/kg before ligation bilateral CCA, immediately ligation bilateral CCA; Sham operated rats tail vein injection Evans blue 50mg/kg, isolates bilateral CCA, but not ligation.After ligation 45min, broken end is got brain, the brain weight in wet base of weighing (decerebellation, oblongata), cerebral tissue is soaked in 4ml Methanamide, and incubation 72h in 45 ℃ of calorstats, gets incubation liquid, by microplate reader, at 620nm place, measure trap, according to standard curve (y=41.214x-0.0035, R2=0.9988), calculate the content of azovan blue in brain, calculate the content (ug/g cutaneous horn weight) of azovan blue in brain.
2.5 mice bilateral common carotid arteries ischemia-reperfusion experiment
2.5.1 grouping, modeling and administration
90 of clean level ICR mices, are divided into 6 groups at random.Be sham operated rats, model group, nimodipine group, the basic, normal, high dosage group of XINNAOXIN JIAONANG.Mice, with after 10% chloral hydrate (350mg/kg, ip) anesthesia, is lain on the back and is fixed on operating-table, routine disinfection, neck median incision, separated bilateral CCA.Model group, positive drug group and XINNAOXIN JIAONANG administration group are closed bilateral CCA10min with noinvasive bulldog clamp folder.Unclamp after bulldog clamp perfusion 10min, then folder closes 10min, then sew up wound after logical.Putting back to insulation in cage raises.The anesthesia of sham operated rats and operation process are identical with model group, but do not block CCA, and observing time is identical with model group.All in modeling process, keeping animal anus temperature 37 ℃ of left and right.Postoperative 3d mice starts gastric infusion: blank group gavage equal-volume normal saline, nimodipine group is 30mg/kg/d, the basic, normal, high dosage group of XINNAOXIN JIAONANG gavage dosage is respectively 170mg/kg/d, 340mg/kg/d, 680mg/kg/d, and every day, gavage was 1 time, successive administration 30d.
2.5.2 diving tower experiment (Step-downavoidancetest)
Passive avoidance response case, base plate is provided with copper grid, can indirect current, voltage is 36V.Place a rubber platform as place of safety for one jiao of copper grid, mice can rest on platform avoids and shocking by electricity.After last administration 1h, start to carry out learning training.Before training, first mice is put into freely movable 3min of case, be familiar with environment, then connect copper grid power supply, continue 5min, incubation period and the errors number in 5min (animal jumps off the number of times of platform) that record jumps off platform for the first time, using this as school grade.After 24h, test, record animal and jump off for the first time the incubation period of platform and the errors number in 5min, using this as Memory result.
2.5.3 channel-type water maze laboratory (watermazetest)
Channel-type water maze is made by black poly (methyl methacrylate) plate, depth of water 22cm, and water temperature is controlled at 25 ℃ of left and right, is divided into outrun, A district, B district, C district, D district.And be provided with 4 cecums, and terminal is provided with step, and animal can be debarked and be hidden drowned danger by step.Before detection, first mice is trained, during training, first animal is placed near terminal step, allow its cat ladder 2 times voluntarily, to be familiar with means of escape.Whole training divided for 4 stages carried out, the first stage: at A place, allow animal learning return terminal from this trip on baffle plate gear; Second stage: baffle plate keeps off at B place, trains as starting point; Phase III: at C place, allow animal learning return terminal from this trip on baffle plate gear; Fourth stage: training from the off.Each stage-training 2 times, available indicating bar guide properly in training process, every stage-training finishes rear rest 2h and carries out the training of next stage again.After all training finishes, allow mice rest 2h, then detect.First mice is put near the cat ladder of terminal, it is climbed up 2 times voluntarily, to be further familiar with environment, be then put in starting point place, record in 3min animal and swim to terminal the omnidistance required time (latency) in district's step place and enter cecum number of times (errortimes) by starting point, as school grade.Can not the person of swimming out of in 3min, meter 3min.Retest after 24h, as Memory result.2.5.4 endothelin-1 (ET-1) in mice plasma, thromboxane B2 (TXB2) and 6-ketone-prostaglandin (6-keto-PGFl α) assay
After behavioristics's experiment finishes, administration after mice fasting 10h, plucks eyeball after administration 1h and gets blood, 3.8% citric acid three sodium solution anticoagulants.The centrifugal 10min of 3000r/min, gets upper strata liquid, in 4 ℃ of preservations, adopts enzyme linked immunosorbent assay (ELISA) to measure each index by test kit description operation sequence.
2.5.5 the preparation of brain tissue homogenate
Mice is plucked eyeball and gets after blood, immediately its de-cervical vertebra is put to death, and takes out cerebral tissue on ice bath, and rinsing in ice-cold normal saline, removes blood, and filter paper is wiped away dry, weighs.Volume ratio adds normal saline and makes 10% tissue homogenate by weight, 2500r/min, and centrifugal 15min, gets supernatant standby.
2.5.6 the mensuration of protein content in mouse brain
Measuring principle: have-NH3+ of protein molecule group, when henna Coomassie brilliant blue developer adds in protein standard liquid or sample, anion on Coomassie brilliant blue dyestuff is combined with albumen-NH3+, makes solution become blueness, by measuring absorbance, can calculate protein content.
Operating procedure: undertaken by test kit description operation sequence.
2.5.7 superoxide dismutase (SOD) is measured
Measuring principle: produce ultra-oxygen anion free radical by xanthine oxidase response system, the latter is oxidized azanol and forms nitrite, presents aubergine under the effect of developer, surveys its absorbance with visible spectrophotometer.While containing SOD in sample, ultra-oxygen anion free radical is had to narrow spectrum inhibitory action, the nitrite forming is reduced, during colorimetric, measure the absorbance of pipe lower than the absorbance of control tube, by formula, calculate the SOD vigor that can obtain in sample.
Operating procedure: referring to SOD test kit description.
2.5.8 malonaldehyde (MDA) is measured
Measuring principle: the malonaldehyde in lipid peroxide catabolite (MDA) can with thiobarbituricacidα-(TBA) condensation, form red product, at 532nm place, have maximum absorption band.
Operating procedure: undertaken by test kit description operation sequence.
2.5.9 glutamic acid (Glu) assay
Measuring principle: glutamic acid+NAD++H2O → α-oxygen 1,3-propanedicarboxylic acid+NADH+NH4+ enzyme
Operating procedure: undertaken by test kit description operation sequence.
2.5.10 acetylcholinesterase (AChE) is measured
Measuring principle: acetylcholinesterase hydrolysis acetylcholine generates choline and acetic acid, choline can react with sulfydryl developer and generate the symmetrical trinitrobenzene of TNB(, 1,3,5-Trinitrobenzene) yellow compound, according to shade, carry out colorimetric assay, the quantity of hydrolyzate choline can reflect the vigor of acetylcholine esterase.
Operating procedure: undertaken by test kit description operation sequence.
2.5.11 nitricoxide synthase (NOS) is measured
Measuring principle: NOS catalysis L-Arg and molecular oxygen reaction generate nitric oxide (NO), and NO and nucleophilicity material generate colored compound, measure absorbance under 530nm wavelength, calculate the vigor of NOS according to the large I of absorbance.
Operating procedure: undertaken by test kit description operation sequence.
2.6 statistical procedures
All data are with mean ± standard deviation<img TranNum="112" file="BDA0000377318350000051.GIF" he="83" img-content="drawing" img-format="GIF" inline="yes" orientation="portrait" wi="154"/>represent, adopt one-way analysis of variance (ANOVA) to experimental data statistical analysis, P<0.05 is for there being statistical significance.
3 experimental results
The impact of 3.1 XINNAOXIN JIAONANG on mice atmospheric closed the survival time under hypoxic condition
Experimental result shows, compares with blank group, and the middle and high dosage group of XINNAOXIN JIAONANG and nimodipine group can obviously increase mice atmospheric closed the survival time under hypoxic condition (P < 0.05, P < 0.05, P < 0.01).And XINNAOXIN JIAONANG low dose group is compared and be there is no significant difference with blank group.In Table 1.
The impact of table 1 XINNAOXIN JIAONANG on mice atmospheric closed the survival time under hypoxic condition
n=10)
Note: with the comparison of blank group, * P < 0.05, * * P < 0.01
The impact of 3.2 XINNAOXIN JIAONANG on the breathing time of dehiscing after mice broken end
Experiment shows, compares with blank group, and the middle and high dosage group of XINNAOXIN JIAONANG and nimodipine group can obviously increase the breathing time (P < 0.01, P < 0.05, P < 0.05) of dehiscing after mice broken end.And XINNAOXIN JIAONANG low dose group is compared and be there is no significant difference with blank group.In Table 2.
The impact of table 2 XINNAOXIN JIAONANG on the breathing time of dehiscing after mice broken end
n=10)
Note: with the comparison of blank group, * P < 0.05, * * P < 0.01
The impact of 3.3 XINNAOXIN JIAONANG on acute incomplete cerebral ischemic model mouse brain index, brain water content
Experiment shows, model group brain water content (P < 0.01) and cerebral index (P < 0.05) and more obviously increases of sham operated rats.Compare with model group, the basic, normal, high dosage group of XINNAOXIN JIAONANG and nimodipine group all can obviously reduce brain water content (P < 0.01, P < 0.05, P < 0.01, P < 0.01) and cerebral index (P < 0.01, P < 0.05, P < 0.05, P < 0.05).In Table 3.
The impact of table 3 XINNAOXIN JIAONANG on acute incomplete cerebral ischemic model mouse brain index, brain water content
n=10)
Note: with sham operated rats comparison, #P < 0.05, ##P < 0.01; With model group comparison, * P < 0.05, * * P < 0.01
The impact of 3.4 XINNAOXIN JIAONANG on acute incomplete cerebral ischemic model mouse brain capillary permeability
As shown in table 4, with sham operated rats comparison, in model group mouse brain, azovan blue content obviously increases (P < 0.01), shows that incomplete cerebral ischemic model mice brain capillary permeability increases.And azovan blue content obviously reduces (P < 0.01, P < 0.05, P < 0.01) compared with model group in the glad middle and high dosage group of heart and brain and nimodipine group mouse brain.
The impact of table 4 XINNAOXIN JIAONANG on acute incomplete cerebral ischemic model mouse brain capillary permeability
n=10)
Note: with sham operated rats comparison, #P < 0.05, ##P < 0.01; With model group comparison, * P < 0.05, * * P < 0.01
4 conclusions
Result of study shows, XINNAOXIN JIAONANG can increase mice atmospheric closed the survival time under hypoxic condition, and increases the broken end breathing time of dehiscing, and prompting XINNAOXIN JIAONANG has certain protective effect to anaerobic environment mice.In addition, XINNAOXIN JIAONANG can obviously reduce brain water content, cerebral index and the brain capillary permeability etc. of cerebral ischemia mice due to bilateral ligation, and prompting XINNAOXIN JIAONANG has certain protective role to experimental cerebral ischemia.
Claims (2)
1. the application of XINNAOXIN JIAONANG in preparation treatment brain ischemia medicament.
2. XINNAOXIN JIAONANG claimed in claim 1, is characterized in that, following parts by weight component, consists of: 3～6 parts of Radix Rhodiolaes, 5～15 parts of Fructus Lyciis, 3～9 parts of Fructus Hippophaes.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104107270A (en) * | 2014-06-19 | 2014-10-22 | 三普药业有限公司 | Application of 'Xinnaoxin' capsule in preparation of drugs for treating chronic stress depression |
| CN104257877A (en) * | 2014-06-19 | 2015-01-07 | 三普药业有限公司 | Applications of Xinnaoxin capsule in preparation of medicines treating cerebral ischemia-reperfusion injury |
| CN105147866A (en) * | 2015-10-13 | 2015-12-16 | 北京普瑞博思投资有限公司 | Traditional Chinese medicine composition for improving cerebral circulation and atherosclerosis and application thereof |
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| CN101002856A (en) * | 2006-01-17 | 2007-07-25 | 尧登全 | Medicine for treating and preventing cardiovascular and cerebrovascular diseases, and its preparing method |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101002856A (en) * | 2006-01-17 | 2007-07-25 | 尧登全 | Medicine for treating and preventing cardiovascular and cerebrovascular diseases, and its preparing method |
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| 曹玉山: "《三普心脑欣胶囊治疗短暂性脑缺血发作观察》", 《中西医结合心脑血管病杂志》 * |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104107270A (en) * | 2014-06-19 | 2014-10-22 | 三普药业有限公司 | Application of 'Xinnaoxin' capsule in preparation of drugs for treating chronic stress depression |
| CN104257877A (en) * | 2014-06-19 | 2015-01-07 | 三普药业有限公司 | Applications of Xinnaoxin capsule in preparation of medicines treating cerebral ischemia-reperfusion injury |
| CN105147866A (en) * | 2015-10-13 | 2015-12-16 | 北京普瑞博思投资有限公司 | Traditional Chinese medicine composition for improving cerebral circulation and atherosclerosis and application thereof |
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Application publication date: 20140122 |