Effect and Mechanism of Didangtang on NLRP3 Inflammasomes in Diabetic Cardiomyopathy Mice / 中国实验方剂学杂志

ABSTRACT

Objective:To investigate the effects of different doses of Didangtang on myocardial inflammatory lesions in diabetic mice. Method:Sixty C57BL/6J mice were randomly divided into normal group （<italic>n</italic>=10） and model group （<italic>n</italic>=50）. The diabetic mice in the model group were established by intraperitoneal injection of high-fat diet combined with streptozotocin （STZ）. After model reproducing， the mice were fed with high-fat diet. After 8 weeks， the cardiac function of the mice was detected by using an ultrasound imaging platform. If the cardiac function decreased， the diabetic cardiomyopathy mice were modeled successfully. The nonmodel mice were eliminated， and finally 40 model mice were modeled. The rats in the model group were randomly divided into model group， low， medium and high dose of Didangtang group（1.5，3，6 g·kg^-1） and simvastatin group（0.001 5 g·kg^-1） according to heart function， with 8 rats in each group. The cardiac function of mice was detected by ultrasound imaging platform， fiber bragg grating（FBG）， triglyceride（TG） and total cholesterol（TC） were detected by automatic biochemical analyzer， hematoxylin-eosin （HE） staining was used to observe the pathological changes of myocardium， and the levels of NOD-like receptor3（NLRP3）， thiomdoxin interaction protein（TXNIP）， cysteinyl aspartate specific proteinase-1（Caspase-1） and Interleukin-1<italic>β</italic>（IL-1<italic>β</italic>） in myocardial tissue， as well as the content of reactive oxygen species（ROS） were detected by Western blot. Result:Compared with the normal control group， the levels of FBG， TC and TG in the model group significantly increased （<italic>P</italic><0.01）； the values of EF and FS significantly decreased （<italic>P</italic><0.01）； the expression of ROS significantly increased （<italic>P</italic><0.05）， and the expressions of NLRP3， TXNIP， Caspase-1 and IL-1<italic>β</italic> in the myocardial tissue significantly increased （<italic>P</italic><0.05）. Compared with the model group， the levels of FBG， TC and TG in the middle and high dose groups of Didangtang and simvastatin groups significantly decreased （<italic>P</italic><0.05）； the EF and FS in each dose group and simvastatin group improved （<italic>P</italic><0.05）， and the change in the middle dose group was more obvious （<italic>P</italic><0.05）. HE staining showed that Didangtang could improve the pathological changes of myocardial tissue in mice， the ROS expression levels of mice in each dose group of Didangtang and simvastatin group significantly reduced， especially in the middle dose group， the expression levels of NLRP3， TXNIP， Caspase-1 and IL-1<italic>β</italic> in each dose group significantly decreased， and the effect of middle dose of Didangtang on reducing expressions of NLRP3， TXNIP and Caspase-1 in myocardial tissue was more obvious， the effect of high dose of Didangtang on reducing the expression of IL-1<italic>β</italic> in myocardial tissue was more obvious. Conclusion:Didangtang can improve myocardial inflammatory lesions in diabetic cardiomyopathy mice by inhibiting the activation of NLRP3 inflammasome.