Effects Of Huazhuo Jiedu Huoxue Tongluo Prescription On The Neuronal Apoptosis And P38MAPK Signal Pathway In Rats Of Cerebral Ischemia Reperfusion Injury

Objective: This study will use Huazhuo Jiedu Huoxue Tongluo prescription to intervene the mice model of cerebral ischemia-reperfusion injury(CIRI) and observe the neurological function deficits scales?the volume of cerebral infarction?the pathological type of the brain tissue?the expression of Caspase-3 and P-P38 MAPK, to explore whether the method inhibit P38 MAPK signaling pathway to regulate apoptosis, further clarify the protective mechanism of Huazhuo Jiedu Huoxue Tongluo prescription on the damaged neurons.Methods: Fifty-four healthy male SD mice were randomly divided into six groups: the sham operation group, the model group, the aspirin group, the low dose of Huazhuo Jiedu Huoxue Tongluo prescription(the low dose group for short), the middle dose of Huazhuo Jiedu Huoxue Tongluo prescription(the middle dose group for short) and the high dose of Huazhuo Jiedu Huoxue Tongluo prescription(the high dose group for short). Mice modes of cerebral ischemia-reperfusion injury were established through improved thread embolism method. After models were successfully established, the drugs were given by gastric perfusion the next day. The physiological saline were given to the mice in the sham operation group and the model group. Aspirin solution were given to the mice in the aspirin group and the respective dose of Huazhuo Jiedu Huoxue Tongluo prescription were given to the low dose group?the middle dose group and the high dose group. The drugs were given once a day for 14 days. Neurologic deficits symptoms score was graded again after the treatment. Then we took out the brain tissue of the mice for the tests. Three of them were stained by TTC to measure the volume of cerebral infarction. The others of each group were taken to observe the pathological type of the brain tissue by HE dyeing?access the expression of Caspase-3 and P-P38 MAPK mRNA by RT-PCR.Results:1 The Neurologic deficits symptoms scores: Compared with the sham operation group, the scores of the model group increased obviously(P<0.05); compared with the model group, the scores of the low dose group and the middle dose group had no difference, the scores of the high dose group and the aspirin group decreased(P<0.05); compared with the low dose group, the score of the high dose group and middle dose group decreased obviously(P<0.05);the score of the high dose group had no significant difference with the aspirin group(P>0.05).2 The pathological morphological changes of the cerebral tissues: The tissues on the cerebral cortex of sham operation group were normal, the cells were arranged regularly and tightly, and there had little dead cells. The ischemic regions were obviously on the cerebral cortex of the model group, tissues were edema and arranged disorderedly, the extracellular space of cells was significantly broadening, a large number of necrotic neuron cells exist; The cerebral morphology on the low dose group was similar to the model group; the necrotic neuron cells on the right side of the cerebral cortex from the middle dose group?the high dose group and the aspirin group were decreased significantly than the model group. There was little difference between the high dose group and the aspirin group, but still existed necrotic neuron cells.3 The volume of cerebral infarction stained by TTC: Compared with the sham operation group, obvious infarctions were visible in the model group and the treatment groups, among them, the low dose group had no significant difference with the model group(P>0.05). Compared with the model group, the volume of infarction was significantly reduced in the middle dose group?the high dose group and the aspirin group(P<0.05); Compared with the aspirin group, the volume of infarction in the high dose group had no obvious change(P>0.05), but the volume of infarction in the low dose group and the middle dose group were more than the aspirin group(P<0.05).4 The expression of Caspase-3 by RT-PCR: The expression of Caspase-3 in the model group was obviously increased than the sham operation group(P<0.05); compared with the model group, the expression of Caspase-3 was decreased in the treatment group(P<0.05); compared with the low dose group, the middle dose group?the high dose group and the aspirin group were decreased significantly(P<0.05);compared with the aspirin group, the middle dose group and high dose group had no difference on the expression of Caspase-3(P>0.05).5 The expression of P-P38 MAPK by RT-PCR: Compared with the sham operation group, the expression of P-P38 MAPK in the model group was obviously increased( P < 0.05); compared with the model group, the expression of P-P38 MAPK was decreased in the treatment group(P<0.05); compared with the low dose group, the expression of P-P38 MAPK in the high dose group and the aspirin group were decreased obviously(P<0.05); but the high dose group had no difference with the aspirin group(P>0.05).Conclusions:1 Huazhuo Jiedu Huoxue Tongluo prescription can significantly improve the pathological morphological damage in the ischemic regions, and reduce the neurologic deficits symptoms score in CIRI model rats.2 Huazhuo Jiedu Huoxue Tongluo prescription can significantly reduce the volume of cerebral infarction in CIRI model rats.3 Huazhuo Jiedu Huoxue Tongluo prescription can inhibit the expression of Caspase-3 and P-P38 MAPK, thus reducing neural cell apoptosis.4 The protctive mechanism of Huazhuo Jiedu Huoxue Tongluo prescription on mice with CIRI maybe related to inhibiton of cell apoptosis, and maybe through P38 MAPK signaling pathway.