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The Protective Effects Of Baicalin On The Ischemic Cerebral Injury And The Mechanism Study

Posted on:2009-11-25Degree:MasterType:Thesis
Country:ChinaCandidate:X XueFull Text:PDF
GTID:2144360245995636Subject:Pharmacology
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Ischemic cerebral vascular disease (ICVD), characterized by high incidence, high recurrence and high mutilation rate, does great harm to human health. It is difficult to study the mechanism as its pathogenesis is complicated , involved in excitatory amino acids injury, oxyradical theory, inflammatory reaction, apoptosis and so on. At present, clinical medication tend to lead to intracranial hemorrhage, brain edema and other problems, and therapeutical effect is not ideal. Therefore, searching for safe and effective drugs by further research on pathogenesis of ICVD will contribute to prevention and cure of this disease greatly.Recent study has revealed that AngⅡis involved in the development of ICVD, but it is still not sure about the mechanism of AngⅡon ischemia reperfusion. Inflammation plays a pivotal role in mediating secondary injury to ischemia reperfusion. Baicalin is the main active component derived from traditional Chinese medicine radix of Scutellariae, which is wildly used for antibacterial treatment, eliminating inflammation and anti-infective therapy in clinical. Studies indicates that Baicalin can protect brain from ischemia-reperfusion injury.In our present study, the ischemia reperfusion injury model was established by middle cerebral artery occlusion (MCAO) to assess the effect of Baicalin by single vena caudalis injection. The protective effect of Baicalin to CIRI was demonstrated using methods from ethology, pathophysiology and molecular biology, and we explored its mechanism, hoping to provide ideas for protection and treatment of CIRI. 1 Effect of Baicalin on infarct volume of rats subjected to ischemia-reperfusion injuryTTC staining for assessment of volume of infarction. The results indicated that the infarction volume were obvious in the model group compared with sham operation group (p<0.01). After the administration of nimodipine 0.4 mg·kg-1, baicalin at the dosage of 50, 100, 200 mg·kg-1 respectively, the infarction volume was decreased significantly (p<0.01,p<0.05, p<0.01, p<0.01). Furthermore, 200 mg·kg-1and exhibited the better therapy results compared with nimodipine (p<0.05).2 Effect of Baicalin on neurological deficits score of rats subjected to ischemia reperfusion injuryThe results indicated that the neurological deficit were obvious in the model group compared with sham operation group (p <0.01). After the administration of baicalin at the dosage of 200 mg·kg-1 , the neurological deficit was eased obviously compared with the model group (p<0.05). Other groups demonstrated no significant differences.3 Effect of Baicalin on path morphology of rats subjected to ischemia reperfusion injuryHE staining result showed that neurons in sham group presented normal cell structures. The neurons in the model group showed paramorphia. After the administration of baicalin at the dosage of 50, 100, 200 mg·kg-1 and nimodipine 0.4mg·kg-1, path morphology injury were markedly ascended.3 Effect of Baicalin on contents of AngⅡin rats subjected to ischemia reperfusion injuryWe collected the supernate of rats' brain and determined the contents of AngⅡby kit. The results showed that after the ischemia-reperfusion injury the contents of AngⅡbecome less in model group compared with sham group (p<0.05). After the administration of baicalin at the dosage of 100, 200 mg·kg-1 and nimodipine 0.4 mg·kg-1, the contents of AngⅡwere increased obviously, (p<0.05) 4 Effect of Baicalin on nuclear translocation of NF-κB p65 in rats subjected to ischemia reperfusion injuryNF-κB p65 are detected in cytoplasm and negative expression in nucleus by immunohistochemistry in sham groups. Compared with sham groups, in model group there are many positive NF-κB p65 expressions in cell nucleus (p<0.01). Baicalin at the dosage of 50, 100, 200 mg·kg-1 and nimodipine 0.4 mg·kg-1 decreased the NF-κB p65 expression in cell nucleus (p<0.01). Baicalin 200 mg·kg-1 inhibited the NF-κB p65 nuclear translocation compared with nimodipine obviously (p<0.05).5 Effect of Baicalin on protein expression of NF-κB p65 in rats subjected to ischemia-reperfusion injuryThe protein expression of the NF-κB p65 is faintly detected in sham groups as indicated by western blot. Whereas, the protein expression of the NF-κB p65 is dramatically increased in ischemia reperfusion injury group. After the administration of baicalin at 50, 100, 200 mg·kg-1 and nimodipine 0.4 mg·kg-1, the increased protein expression is markedly down-regulated (p<0.01). Furthermore, 200 mg·kg-1 baicalin eased the protein expression obviously compared with nimodipine (p<0.05).6 Effect of Baicalin on the mRNA levels of NF-κB p65 in rats subjected to ischemia reperfusion injurySemiquantative RT-PCR withβ-actin as an internal control was used to detect the NF-κBp65 mRNA expression in the ischemic cortex. The NF-κB p65 mRNA expression were increased obviously in model group compared with sham group. The NF-κB p65 mRNA expression were significantly diminished after the administration of baicalin at 50,100, 200 mg·kg-1 and nimodipine 0.4 mg·kg-1 (p<0.01). Furthermore, 200 mg·kg-1 baicalin decreased the mRNA levels compared with nimodipine markedly (p<0.05).
Keywords/Search Tags:Ischemia-reperfusion injury, Baicalin, AngiotensinⅡ, Nuclear-factor p65
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