Study On Myocardial Protective Effect Of Wanjin Wenwu Decoction Of The Traditional Chinese Korean Medicine In Diabetic Cardiomyopathy Rats Based On Nrf2/HO-1/NLRP3 Signaling Pathway

Objective:To investigate the effect of Wanjin Wenwu Decoction（WWD）of Traditional Chinese Korean Medicine（TCKM）on diabetic cardiomyopathy injury in rats and the possible mechanism of regulating Nrf2/HO-1/NLRP3 signaling pathways.Methods:60 healthy SD male rats were fed normal diet first,and then the rats except the normal group were fed with high-fat and high-sugar diet.Each group was given a one-time intraperitoneal injection according to the modeling requirements.Streptozotocin(STZ,35 mg·kg^-1)was injected and the blood glucose was measured on the 3rd and 7th days.The diabetes models were successfully established with the high blood glucose（≥11.1 mmol/L）.The normal group was given a one-time intraperitoneal injection of an equal volume of sodium citrate buffer.The rats were randomly divided into normal group（Control）,diabetic cardiomyopathy group（DCM）,metformin group（MET）,WWD low-dose group（WWDL）,and WWD high-dose group（WWDH）.Except for the Control group,the other groups continued to be fed with high-fat and high-sugar.Changes in blood glucose and body weight were checked weekly and administered for 8 weeks.Control group and DCM group were given an equal volume of normal saline,and the gentiment dose was calculated by the weight of the other groups;The MET group was given metformin(200 mg·kg^-1),and the WJDL group and WJDH group were given different doses of Wanjin Wenwu Decoction(300,600 mg·kg^-1)by gavage,respectively.Blood glucose,body weight,OGTT glucose tolerance changes and the area under the blood glucose curve（AUC）were measured.The pathological changes of rat myocardial tissue were observed by HE staining;the levels of IL-6,GSH-Px,c Tn-I,TNF-α,ROS were determined by ELISA kits,as well as LDH,AST,MDA,SOD in serum;The protein levels of Nrf2,HO-1,TXNIP,NLRP-3 and cleaved-Capase1 in cardiomyocyte tissue were observed by Western blot.Results:Compared with the control group,the blood glucose,heart-to-body ratio,OGTT and AUC values in the DCM group were significantly increased（P<0.05）;HE staining showed that the myocardial cells were arranged disorderly,the nuclei were sparse and irregular,and the nucleus and the interstitium were enlarged,the tissue fiber structure was not clear.The values of GSH-Px and SOD in serum were significantly decreased（P<0.05）,and the values of IL-6,c Tn-I,TNF-α,ROS,LDH,AST and MDA were significantly raised（P<0.05）;the protein expressions of Nrf2 and HO-1in myocardial tissue were significantly reduced（P<0.05）,and the protein contents of TXNIP,NLRP-3 and cleaved-Capase1 were significantly increased（P<0.05）.Compared with the DCM group,the blood glucose,heart-to-body ratio,OGTT and AUC values of the MET group,WJDL group and WJDH group were all decreased（P<0.05）;HE staining showed that the myocardial cells and nuclei of the MET group and the WJDH group were arranged in a neat and orderly manner,and the tissue fiber structure was clear and complete.;the contents of GSH-Px and SOD in serum of MET group,WJDL group and WJDH group all enhanced（P<0.05）,and the contents of IL-6,c Tn-I,TNF-α,ROS,LDH,AST and MDA in serum were all lessened（P<0.05）.The levels of Nrf2 and HO-1 in the MET group were attenuated and improved in the WJDL group and WJDH group with depression of TXNIP,NLRP-3 and cleaved-Capase1 protein expression（P<0.05）.Conclusion:WWD could improve diabetic cardiomyopathy injury by inhibition of inflammation and oxidative stress,and its possible mechanism may be related to the regulation of Nrf2/HO-1/NLRP3 signaling pathways.