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The Influence of Procyanidins on the Metabolism Dysbolism and the Expression of Acid-sensing Ion Channe 1a after Cerebral Ischemia-Reperfusion in Rats

Author: ChenXiangHong
Tutor: ZhangYan;FengGuoQing
School: Zhengzhou University
Course: Pharmacology
Keywords: Proanthocyanidins Ischemia-reperfusion Acid-sensitive ion channels Metabolic disorders
CLC: R285.5
Type: Master's thesis
Year: 2008
Downloads: 32
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Abstract


Objective: cerebral ischemia is a common clinical acute cerebrovascular disease with high morbidity and mortality. Clinical lack of effective the ideal treatment drugs, so finding an effective neuroprotective drugs in order to reduce the incidence of complications is still the focus of the study of cerebral ischemia. More researchers focus on the development of herbal medicine as a neuroprotective drug ingredients Botanicals has multiple and wide-ranging role, no or only a very low side effects and other advantages and has a good prospect. Proanthocyanidins (procyanidin, PC) is a natural polyphenolic compounds with strong antioxidant effect, in recent years, studies have shown that the PC through antioxidant, anti-inflammatory to play the cerebral protective effects in brain ischemia-reperfusion injury. Cerebral ischemia-reperfusion injury is a complex pathophysiological process, often accompanied by metabolic disorders, and in recent years, studies found that the acid-sensitive ion channels (acid-sensing ion channels, ASICs) in ischemic brain injury in the pathophysiological process plays important role. PC can play through the intervention of ASICs and brain tissue metabolism brain protection, at home and abroad has not been reported. In view of this, the research through the establishment of rat reversible middle cerebral artery occlusion (MCAO) model mainly observed the PC in cerebral ischemia-reperfusion injury, metabolic disorders of the brain tissue and ASIC1a subunit, to further explore the neuroprotective the mechanism of action, and application-targeted neuroprotective drugs provide a theoretical basis for the clinical findings. : 160 weight of 270-300 grams of healthy adult male SD rats were randomly divided into sham group, model group and low PC (50,100,200 mg / kg) of the medium and high dose groups. 30min before surgery with intraperitoneal administration, injection the proanthocyanidins solution of different concentrations, and cerebral ischemia 2h after repeated administration, sham group and model group were given saline. Using a modified Zea-Longa intraluminal reversible cerebral ischemia model in rats. Longa score after cerebral ischemia 2h 24h of reperfusion neurological score, then the rats were decapitated and the brain, and remove the right side of the brain tissue, brain water content was determined by wet and dry quality eight randomly selected groups; 8 for pathological morphology observed; 8 for the determination of the content of lactic acid, the of Na -K ATPase and Ca 2 ATPase activity; ASIC1a mRNA expression in rat hippocampal tissue detected by RT-PCR method. Results: ① model group of neurological function score increased (P <0.05) compared with sham group; PC, the high-dose group compared with the model group decreased (P <0.05), and no significant difference between the two groups (P> 0.05 ), low the PC-dose group with model group showed no significant difference (P> 0.05). ② cerebral ischemia 2h reperfusion 24h when compared with sham group, model group, brain water content was significantly higher (P <0.05); the PC, the middle dose group compared with the model group, brain water content was lower (P <0.05) , and between the two groups was no significant difference (P> 0.05), low PC-dose group compared with the model group, no significant difference (P> 0.05). ③ sham group cells and stromal no obvious abnormalities, model group, cell swelling, contour unclear, vacuolar degeneration, of nuclear stained and interstitial edema, cell gap increases, the decrease in the number of PC-dose group above pathological changes have improved to varying degrees, including PC, the effect is more obvious in dose group. ④ cerebral ischemia 2h 24h of reperfusion compared with sham group, model group, brain tissue lactate content increased (P <0.05); the PC, in the high-dose group compared with the model group decreased (P <0.05). ⑤ model group Na -K > ATPase activity compared with the sham-operated group reduce (P <0.05); PC in the high-dose group compared with the model group increased (P <0.05) and between the two groups was no significant difference (P> 0.05), low-dose group and the model group showed no significant difference (P> 0.05). The model group Ca 2 ATPase activity compared with the sham surgery group decreased (P <0.05); only the high-dose group Ca 2 ATPase activity is higher than the model group. ASIC1a mRNA relative expression level ⑥ model group than in the sham group increased (P <0.05); the PC high dose group compared with the model group decreased (P <0.05), no significant difference in the low-dose group compared with the model group. Conclusion: ① the PC effectively reduce cerebral ischemia - reperfusion injury, which play a neuroprotective effect. ② PC neuroprotective mechanism may be related to cerebral edema, improve brain cell metabolism and inhibit the expression of acid-sensing ion channels ASIC1a.

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