补阳还五汤对脑缺血再灌注损伤小鼠RhoA/ROCK通路的影响

Effects of Buyang Huanwu Decoction on RhoA/ROCK Pathway after Cerebral Ischemia/Reperfusion Injury in Mice

    摘要
  • 摘要:
      目的  探讨补阳还五汤对脑缺血再灌注损伤小鼠小胶质细胞P2Y12受体介导的RhoA/ROCK炎症信号通路的影响。
      方法  将C57BL/6J小鼠随机分为Sham组、MCAO组、BYHW-L(低剂量, 6.5 g·kg-1)组、BYHW-H(高剂量, 26 g·kg-1)组、BYHW-H+MRS2395组, 构建大脑中动脉闭塞模型(Middle cerebral artery occlusion, MCAO), 通过Longa生物学评分、TTC染色评估小鼠神经功能损伤情况; 通过免疫荧光双标染色法、qPCR方法检测小胶质细胞M1、M2表型极化情况; 通过Western blot法检测P2Y12受体介导的RhoA/ROCK通路蛋白的表达情况。
      结果  与MCAO组相比, 补阳还五汤能改善脑缺血再灌注损伤小鼠的神经功能损伤(P＜0.05)和减小梗死体积(P＜0.05, P＜0.01), 增加小胶质细胞从M1型向M2型极化(P＜0.05, P＜0.01), 抑制P2Y12受体蛋白表达(P＜0.05, P＜0.01), 阻断P2Y12介导的RhoA/ROCK通路及通路下游的p38 MAPK磷酸化(P＜0.05, P＜0.01), 抑制炎症损伤(P＜0.05, P＜0.01)。加入P2Y12受体抑制剂MRS2395未阻断补阳还五汤改善神经功能损伤及抗炎作用。
      结论  补阳还五汤可通过P2Y12受体介导的RhoA/ROCK炎症信号通路改善小鼠脑缺血再灌注后的脑损伤, 还可通过其他途径及通路发挥抗炎作用, 但具体机制有待进一步探索。

     

    Abstract:
      OBJECTIVE  To investigate the effect of Buyang Huanwu Decoction on microglial P2Y12 receptor-mediated RhoA/ROCK inflammatory signaling pathway in mice with cerebral ischemia/reperfusion (I/R) injury.
      METHODS  The C57BL/6J mice were randomly assigned to the Sham group, MCAO group, BYHW-L (low-dose, 6.5 g·kg-1) group, BYHW-H (high-dose, 26 g·kg-1) group, and BYHW-H+MRS2395 group. The middle cerebral artery occlusion (MCAO) model was constructed, and the neurological impairment of the mice was evaluated by Longa biological score and TTC staining. The phenotypic polarization of microglia towards M1 or M2 was detected by immunofluorescence staining and qPCR. The protein expression levels of factors in RhoA/ROCK pathway mediated by the P2Y12 receptor were detected by Western blot.
      RESULTS  Compared with MCAO group, Buyang Huanwu Decoction could reduce the neurological impairment (P < 0.05) and infarct volume of I/R injured mice (P < 0.05, P < 0.01), increase the polarization of M1 to M2 in microglia cells (P < 0.05, P < 0.01), inhibit the expression of P2Y12 receptor protein (P < 0.05, P < 0.01), block the P2Y12-mediated RhoA/ROCK pathway and p38 MAPK phosphorylation in the downstream pathway (P < 0.05, P < 0.01), and inhibit the inflammatory damage (P < 0.05, P < 0.01). The P2Y12 receptor inhibitor MRS2395 did not block the anti-inflammatory effect of Buyang Huanwu Decoction.
      CONCLUSION  Buyang Huanwu Decoction may help to improve brain function after cerebral I/R injury in mice through P2Y12-mediated RhoA/ROCK inflammatory signaling pathway, it may also play an anti-inflammatory role through other pathways, but the other mechanisms need further exploration.

     

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