| Objective: To investigate the mechanism that Shi Da La Zhi Pill can effectively reduce the reperfusion injury in rats with cerebral ischemia through the intervention in rats with cerebral ischemia-reperfusion by " Shi Da La Zhi Pill " which is the classic prescription drug that can treat stroke in “Hui hui prescription”.Methods: A total of 204 SD male rats were randomly divided into the blank control group,sham-operated group,model group,Nimodipine group,and low-medium-high-dose Shi Da La Zhi Pill.The model group,Nimodipine group,and high-medium-low-dose Shi Da La Zhi Pill were made middle cerebral artery occlusion(MCAO)models by suture-occluded method,they were reperfused 2h after ischemia,and the neurological function scores were obtained by Garcia JH method on the 1st,3rd,and 7th day after operation.The number of newborn NSCs was observed by Brdu/Nestin double immunofluorescent staining;The relative amount of mRNA of the Nestin gene was detected by RT-PCR;The expression of Nestin protein and Jagged1 protein was detected by WB.Results:1.Synchronous Comparison of the blank control group and sham-operated group: There is no statistically significant difference in the Garcia JH score,number of newborn NSCs and relative amount of mRNA of the Nestin gene,as well as the amount of Nestin and Jagged1 protein expression.(P >0.05)2.Compared with the blank control group and sham-operated group,The Garcia JH score,number of newborn NSCs and relative amount of mRNA of the Nestin gene,as well as the amount of Nestin and Jagged1 protein expression all are higher in the model group,Nimodipine group,and low-medium-high-dose Shi Da La Zhi Pill groups.(P <0.05).3.Compared with the group itself on 1d,Garcia JH score,number of newborn NSCs and relative amount of mRNA of the Nestin gene,as well as the amount of Nestin and Jagged1 protein expression all had significantly increased in the model group,Nimodipine group,and low-medium-high-dose Shi Da La Zhi Pill groups intragastrically administrated on 3d and 7d.(P <0.05)4.Compared with group itself intragastrically administrated on 3d,Garcia JH score,number of newborn NSCs and relative amount of mRNA of the Nestin gene,as well as the amount of Nestin and Jagged1 protein expression all had significantly increased in the model group,Nimodipine group,and low-medium –high-dose Shi Da La Zhi Pill groups intragastrically administrated on 7d.(P <0.05)5.Synchronously Compared with model group,Garcia JH score,number of newborn NSCs and relative amount of mRNA of the Nestin gene,as well as the amount of Nestin and Jagged1 protein expression all are higher in Nimodipine group,and low-medium –high-dose Shi Da La Zhi Pill groups.(P <0.05)6.Synchronously Compared with Nimodipine group,the Garcia JH score,number of newborn NSCs and relative amount of mRNA of the Nestin gene as well as the amount of Nestin and Jagged1 protein expression of the low-dose Shi Da La Zhi Pill group are lower(P <0.05)while the those indexes are higher in high-dose Shi Da La Zhi Pill group(P <0.05).All above indexes in medium-dose Shi Da La Zhi Pill group are on par with the those of Nimodipine group.(P >0.05)Conclusion:1.Shi Da La Zhi Pill can effectively improve the Garcia JH scores and improve the neurologic impairment symptom of rats with focal cerebral ischemia-reperfusion.2.Shi Da La Zhi Pill can promote the proliferation of NSCs in hippocampus of rats with focal cerebral ischemia-reperfusion.3.Shi Da La Zhi Pill can promote the proliferation of NSCs in hippocampus of rats and reduce the cerebral ischemia-reperfusion injury(CIRI)of rats,which may be related to the activation of Notch signal transduction pathway. |
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