香芹酚通过MAPK/ERK信号通路对缺血再灌注后脑损伤大鼠的保护作用

Carvacrol protects against cerebral ischemia-reperfusion injury in rats through MAPK/ERK signaling pathway

目的探索香芹酚(CAR)预处理对急性脑缺血再灌注损伤(CI/R)大鼠的影响,及相关分子机制研究。方法 60只SD大鼠随机分为5组:对照组,模型组和CAR 10 mg/kg组,CAR 20 mg/kg组,CAR 50 mg/kg组,每组12只。CAR各浓度组在CI/R制作前6 h给予不同浓度CAR腹腔注射预处理,对照组和模型组只注射等量0. 9%氯化钠溶液。再灌注24 h后处死各组大鼠,取出相应部位脑组织进行分析检测各组大鼠脑组织三磷酸腺苷(ATP)酶活性、钙离子(Ca^(2+))含量,TUNEL染色法计算凋亡细胞数,以及通过Western blot法检测p-MEK2及p-ERK1/2蛋白表达。结果CAR能显著降低CI/R后大鼠脑组织Ca^(2+)含量(P <0. 05),但对ATP酶活性物显著影响(P> 0. 05); TUNEL染色结果显示,CAR能明显降低CI/R后大鼠脑细胞凋亡数,与模型组比较,差异有统计学意义(P <0. 05); Western blot显示,CAR能显著抑制p-MEK2及p-ERK1/2蛋白表达,与模型组比较,差异有统计学意义(P <0. 05)。结论 CAR可通过MAPK/ERK信号通路抑制CI/R后脑细胞凋亡,从而发挥保护作用。

Objective To explore the effects of carvacrol(CAR)on the cerebral ischemia-reperfusion injury(CI/R)in rats and to study the related mechanism.Methods 60 SD rats were divided into 5 groups:the control group(n=12),model group(n=12)and CAR 10mg/kg(n=12),CAR 20 mg/kg(n=12),CAR 50 mg/kg group(n=12).CAR concentration groups were pretreated with different concentrations of CAR for 6 h before CI/R preparation.The control group and the model group were injected with only 0.9%sodium chloride solution.Adenosine triphosphate(ATP)enzyme activity and calciumion(Ca 2+)content were detected after ischemia-reperfusion for 24h.Meanwhile,Number of apoptotic cells was counted via TUNEL method,and the protein expression of p-MEK2 and p-ERK1/2 were valued by western blot.Results CAR could significantly suppress the Ca 2+content(P<0.05),but there was no significant effect on the activity of ATP enzyme(P>0.05).Besides,TUNEL methods revealed that CAR could markedly decrease the apoptosis number of brain cells(P<0.05).Besides,western blot demonstrated that CAR could effectively suppress the p-MEK2 and p-ERK1/2 expression,compared with the model group(P<0.05).Conclusion CAR can inhibit the apoptosis of brain cells after CI/R through MAPK/ERK signaling pathway.