The Effect Of Xinnaotongluoye On The Cytokines And Bcl-2,p53 Of Apoptotic Genes In The Brain Of Rats With Acute Focal Cerebral Ischemia

Objective: To observe the effect of XinNaoTongLuoYe on pathomorphism change,ultrastructure,cytokines,apoptotic gene Bcl-2 and p53 of acute phase cerebral ischemia in rats by establishing the model of focal cerebral ischemia, investigate the mechanism of action and provide a reliable theoretic basis for this therapy.Methods: The healthy SD rats were randomly divided into five groups: sham-operated group, cerebral ischemia group (named the model group), BuChangNaoXinTong group (named the control group), high-dose group of XinNaoTongLuoYe (named the high-dose group) and low-dose group of XinNaoTongLuoYe (named the low-dose group). The rat models of acute focal cerebral ischemia with middle cerebral artery occlusion were established by inserting nylon thread. After 48 hours of cerebral ischemia, we detected the changes of the contents of cerebral IGF-1and IL-8 by immunology and the cerebral VEGF and ICAM-1 by Enzyme-linked immunosorbent assay. Meanwhile, we observed the ultrastructural changes by electron microscope and pathomorphological changes in the cerebral tissue by HE. Besides, we detected the apoptosis of nerve cells by TUNEL and the expression of relevant controlling gene Bcl-2 and p53 and the expressing changes of BFGFmRNA and Es-mRNA by RT-PCR.Results: (1)Compared with model group, the content of IL-8 in brain of each dose group of XinNaoTongLuoYe decreased and the difference was significant(P<0.01)with the most markedly changing of high-does group,the difference among high-dose group ,low-dose group and control group was insignifican(tP>0.05).The content of ICAM-1 in brain of each dose group of XinNaoTongLuoYe decreased and the difference was significant(P<0.01)with the most markedly changing of high-does group,the difference between high-dose group and control group was significant(P<0.01).(2)Compared with model group, the content of IGF-1 in brain of each dose group of XinNaoTongLuoYe increased and the difference was significant(P<0.01)with the most markedly changing of high-does group,the difference between high-dose group and control group was insignificant(P>0.05).The content of VEGF in brain of each dose group of XinNaoTongLuoYe increased and the difference was significant(P<0.01)with the most markedly changing of high-does group,the difference among high-dose group, low-dose group and control group was significan(tP<0.01).(3)HE dyeing: Compared with model group ,nerve cells edema and the inflammation of capillary vessel in the focus each dose group of XinNaoTongLuoYe was ameliorated and the change of high-does group was most remarkable.(4)Electron microscope : Compared with model group , the impairment in the focus of each dose group of XinNaoTongLuoYe was ameliorated and the change of high-does group was most remarkable.(5)Compared with model group, the apoptotic rate of each dose group of XinNaoTongLuoYe decreased and the difference was significan(tP<0.01or P<0.05)with the most markedly changing of high-does group,the difference among high-dose group , low-dose group and control group was significant(P<0.01 or P<0.05).The expression of Bcl-2 in brain of each dose group of XinNaoTongLuoYe increased, the expression of p53 in brain of each dose group of XinNaoTongLuoYe decreased and the difference was significant(P<0.01)with the most markedly changing of high-does group, the difference among high-dose group ,low-dose group and control group was significant (P<0.01).(6)Compared with model group, the expression of BFGFmRNA in brain of each dose group of XinNaoTongLuoYe increased and the difference was significant(P<0.01)with the most markedly changing of high-does group,the difference among high-dose group , low-dose group and control group was significant(P<0.01).The expression of E-smRNA in brain of each dose group of XinNaoTongLuoYe decreased and the difference was significant(P<0.01)with the most markedly changing of high-does group,the difference between high-dose group and control group was insignificant(P>0.05).Conclusion:(1)XinNaoTongLuoYe can reduce content of IL-8,ICAM-1 in cerebral tissue during cerebral ischemia and alleviate the level of inflammation.(2) XinNaoTongLuoYe can increase content of IGF-1 and VEGF in brain tissue which may be the endogenous protective mechanism during the ischemia situation.(3)XinNaoTongLuoYe can lessen the neuronal impairment.(4)XinNaoTongLuoYe can repress apoptotic rate, promote Bcl-2 expressing and inhibit p53 expressing which indicates that the effecting of Xin NaotongluoYe on repressing apoptosis is related to the regulation on the expressing of Bcl-2 and p53.(5)XinNaoTongLuoYe can promote the expressing of BFGFmRNA in brain tissue of cerebral ischemia rats,incease content of cerebral NTF in transcriptional level, inhibit expressing of Es-mRNA in brain tissue of cerebral ischemia rats and alleviate the damage of inflammation in transcriptional level to reach to ameliorate the degree of ischemia damage in effect.