Effect of Rhein on AQP4 and Microglia Mediated Inflammatory Response in Cerebral Ischemia Rats / 中国实验方剂学杂志

ABSTRACT

Objective:To investigate the effect of rhein on aquaporin 4 （AQP4） and brain edema after cerebral ischemia and the role of microglia-mediated inflammation in this process. Method:The modified thread embolization method was selected to establish the cerebral ischemia model of the right middle cerebral artery embolism （MCAO） in rats. The rats were divided into sham operation group， model group， minocycline group， and high， medium and low-dose rhein groups （3.46，1.73，0.865 mg·kg^-1）. The neurobehavioral function was measured by a modified neurobehavioral score. Wet and dry weight methods were used to measure the changes of water content in brain tissue of rats with cerebral ischemic injury. Western blot was used to detect the expressions of interferon-<italic>γ</italic> （IFN-<italic>γ</italic>） and interleukin-2 （IL-2） in the peripheral ischemic area of rats in each group. Immunofluorescence double labeling method was used to detect the expressions and localization of microglia fine markers Iba-1 and AQP4. Result:Compared with the sham operation group， neurological function score and water content on the side of brain tissue injury of the model group were significantly increased （<italic>P</italic><0.05）. Compared with the model group， the neurological function score and the water content of the brain tissue of each drug group were reduced （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with sham operation group， the protein expressions of IFN-<italic>γ</italic> and IL-2 in the model group increased significantly （<italic>P</italic><0.05）. Compared with the model group， the protein expressions of IFN-<italic>γ</italic> and IL-2 in the peripheral area of cerebral ischemia of each drug group were significantly improved （<italic>P</italic><0.05， <italic>P</italic><0.01）. Immunofluorescence double staining results showed that compared with the sham operation group， the model group showed significant increase in the fluorescence expression of AQP4 protein on activated microglia， while each drug group could reduce the fluorescence expression of AQP4 protein on activated microglia， different levels of activated microglia markers Iba-1 and AQP4 were co-localized in the peripheral area of cerebral ischemia in each group. Conclusion:Rhein could reduce the degree of brain edema caused by cerebral ischemic injury， and its mechanism may be related to the inhibition of microglia-mediated neuroinflammation and the down-regulation of AQP4 expression.