参芍口服液调控TLR4/MyD88通路改善糖尿病大鼠心肌炎症损伤

Shenshao decoction improves myocardial inflammatory injury in diabetic rats by regulation of TLR4/MyD88 pathway

目的探讨参芍口服液在糖尿病心肌病(diabetic cardiomyopathy,DCM)大鼠结构功能损伤中的作用及其可能机制。方法一次性腹腔注射大剂量链脲佐菌素诱导糖尿病大鼠模型。测定血浆心肌酶(CK、LDH)、超敏C反应蛋白(hs CRP)的变化,左心室插管测定大鼠心功能,苏木素-伊红染色、透射电镜观察大鼠心肌病理改变,免疫组织化学法检测Toll样受体4(TLR4)、髓样分化蛋白(My D88)及核因子κB P65(NF-κB P65)表达。结果治疗6周后,DCM大鼠左心室舒张和收缩功能明显改善;心肌纤维及线粒体肿胀、断裂、坏死减少,结构紧密,排列整齐;CK、LDH、hs CRP含量降低(P<0.05),且hs CPR与CK、LDH呈正相关(r=0.753,r=0.819,P<0.05);TLR4、My D88、NF-κB P65表达明显下调(P<0.05)。而参芍口服液干预的正常大鼠上述指标无明显改变(P>0.05)。结论参芍口服液可减轻糖尿病心肌病大鼠心肌损伤,改善心脏舒张和收缩功能,其机制可能与抑制TLR4/My D88信号通路诱导的炎症反应有关。

Objective To investigate the improving effects of Shenshao decoction on myocardial structure and function in diabetic cardiomyopathy,and its effect on expression of TLR4/My D88-dependent pathway signal in diabetic cardiomyopathy. Methods Diabetes mellitus was induced in 8-week-old male Wistar rats by a single intraperitoneal injection of streptozotocin. The changes of plasma myocardial enzyme（ CK,LDH） and high sensitive C reactive protein（ hs CRP） were measured. Cardiac function was measured by left ventricular intubation. Hematoxylin and eosin staining and electron microscopy were used to observe the changes of myocardial morphology and ultrastructure in rats. Expression of Toll-like receptor 4（ TLR4）,myeloid differentiation protein 88（ My D88）,and nuclear factor-κB P65（ NF-κB P65） were tested by immunohistochemistry. Results After 6 weeks of treatment,the left ventricular diastolic and systolic functions were obviously improved; the degrees of myocardial fibers and mitochondrial damage were obviously relieved; the content of CK,LDH and hs CRP decreased（ P〈0. 05）,and hs CPR was positively correlated with CK and LDH（ r = 0. 823,r =0.819,P〈0.05）.The expressions of TLR4,My D88,NF-κB P65 were significantly decreased（P〈0.05）.There was no significant difference in the above mentioned indicators between the control group and control＋Shenshao decoction group（P〈0.05）.Conclusions Shenshao decoction can reduce the myocardial injury in diabetic cardiomyopathy and improve cardiac diastolic and systolic functions.The mechanism may be related to attenuated inflammation by TLR4/My D88dependent signaling pathway.