通心络胶囊对糖尿病小鼠视网膜p38MAPK信号通路的影响

Effects of Tongxinluo capsule on p38 mitogen-activated protein kinase signal pathway in retina of diabetic mice

目的观察通心络胶囊对糖尿病小鼠视网膜p38丝裂原活化蛋白激酶(p38MAPK)信号通路的影响,探讨其视网膜保护作用的可能机制。方法 KK/Upj-Ay小鼠40只随机分为糖尿病模型组、通心络低、中、高剂量组,每组10只,另设C57BL/6(C57)小鼠10只作为对照组。按照分组给予不同剂量处理因素,疗程3个月,观察体质量,测定空腹血糖(FBG),取眼球行HE染色,Western-blot检测视网膜p38MAPK、JNK、ERK总蛋白及磷酸化p38MAPK、JNK、ERK(p-p38MAPK、p-JNK、p-ERK)的表达。结果与对照组比较,模型组体质量、FBG及p-p38MAPK、p-JNK、pERK表达均显著增高,通心络胶囊能够减轻视网膜病理损伤,降低p-p38MAPK表达(P<0.05),而不影响体质量、FBG及p-JNK、p-ERK表达(P>0.05);且各组p38MAPK、JNK、ERK总蛋白表达差异无统计学意义(P>0.05)。结论 p38MAPK信号通路可能参与了糖尿病视网膜损害的发生发展。通心络胶囊可减轻糖尿病小鼠视网膜病理损伤,其机制可能与降低p38MAPK蛋白磷酸化水平有关。

Objective To observe the effects of Tongxinluo capsule on p 38 mitogen-activated protein kinase （p38MAPK） signal pathway in retina of diabetic mice in order to explore the possible mechanism of the protective effect of Tongxinluo capsule on retina .Methods Forty KK/Upj-Ay mice were randomly divided into diabetes model group , diabetic model with Tongxinluo （low-dose,median-dose,high-dose） groups,with 10 mice in each group,at the same time,10 C57BL/6 mice were selected as control group .After 3 months,the mice were sacrificed and were weighed .The fasting blood glucose （FBG） was measured.The retina was subjected to HE staining.The expression levels of total p38MAPK,phosphorylated p38MAPK（p-p38MAPK）,total JNK,phosphorylated JNK（p-JNK）,total ERK,phosphorylated ERK（p-ERK） in retina were detected by Western blotting .Results As compared with those in control group , the average body mass and the expression levels of p-p38MAPK, p-JNK, p-ERK were significantly increased in model group .Tongxinluo capsule could relieve retinal pathological damage and reduce the expression levels of p-p38MAPK in retina of diabetic mice （ P〈0.05）,however,which had no effect on body weight,FBG and expression levels of p-JNK,p-ERK（ P 〉0.05）.Furthermore,there were no significant differences in the expression levels of p38MAPK,JNK and ERK proteins among groups （ P 〉0.05）.Conclusion The p38MAPK signal pathway may be involved in the pathogenesis and development of diabetic retina injury .Tongxinluo capsule can relieve retina pathological damage in diabetic mice , which may be related with down-regulating phosphorylation of p38MAPK protein.