Therapeutic Effects of Inhibition of the TLR4/NF-κB Pathway by Total Alkaloids of Rhizoma Corydalis on Diabetic Cardiomyopathy in Rats
Objective:To investigate the therapeutic effects of total alkaloids of Total Alkaloids of Rhizoma Corydalis(TAC)in diabetic cardiomyopathy(DCM)rats,and to explore its effect of the Toll-like receptor 4/nuclear transcription factor κB(TLR4/NF-κB)pathway.Methods:SPF grade male SD rats were fed with high-fat and high-sugar chow+intraperitoneal injection of STZ to prepare DCM model.Rats can be divided into five groups as normal group(Con)without model preparation,do not use the drug intervention;Model group(Mod)was used for model preparation without drug intervention;TAC high(H-TAC),medium(M-TAC)and low(L-TAC)dose groups were treated with high(14 mg/kg),medium(10 mg/kg)and low(7 mg/kg)concentration TAC solution.The duration of model preparation was 16 weeks,and the drug intervention lasted for 28 days.Observe the differences in general characteristics of rats and analyze the changes in blood glucose levels in rats before and after modeling and treatment.Pathological changes of myocardial tis-sues were observed by HE staining,myocardial enzymes creatine kinase(CK),creatine kinase isoenzyme(CK-MB),and lactate dehydro-genase(LDH)were detected by biochemical method,and the levels of tumor necrosis factor-alpha(TNF-alpha),interleukin-6(IL-6),and interleukin-1 beta(IL-1β)were detected by ELISA method in myocardial tissues.(IL-1β)levels.TLR4,Myeloid Differentiation factor 88(MyD88)and NF-κB were detected in myocardial tissues by immunoprotein blotting and immunohistochemistry.Results:After observ-ing that Mod rats were relatively emaciated,depressed and less active,with fluffy body hair losing luster,and drinking and urinating more,the rats in each treatment group showed improvement in body condition,mental state,body hair luster,as well as drinking and uri-nating.The results of blood glucose test showed that the blood glucose level of Mod rats was significantly higher than that of Con rats after modeling,while the blood glucose level of each treatment group was significantly lower than that of Mod rats,and showed a quanti-tative and effective relationship(all P＜0.05).HE staining results showed that the arrangement of myocardial fibers was disordered in Mod rats,with a significantly enlarged myocardial interstitial space,uneven cytoplasmic staining,increased cytosolic nucleus condensation,and a localized infiltration of inflammatory cells,while the above pathological changes were significantly less severe in the treatment groups compared to Mod rats,and showed a quantitative and effective relationship.CK,CK-MB,LDH test results showed that Mod myocardial enzyme levels were significantly higher,while the levels of myocardial enzymes in each treatment group were significantly lower than those of Mod,and showed a quantitative relationship(all P＜0.05).TNF-α,IL-6,IL-1β test results showed that the expression of inflammatory factors in Mod was significantly higher than that in Con,while the expression of inflammatory factors in each treatment group was significantly higher than that in Mod.Inflammatory factor expression was significantly lower than Mod(all P＜0.05).TLR4/NF-κB protein assay showed that Mod protein expression was significantly higher than Con,while protein expression was signifi-cantly lower than Mod in each treatment group(all P＜0.05).Conclusion:TAC can reduce the blood glucose level,reduce the levels of in-flammatory factors,improve myocardial function and pathological damage in DCM rats,which may be related to the TLR4/NF-κB sig-naling pathway and the inhibition of inflammatory cascade reaction.
Total Alkaloids of Rhizoma CorydalisTLR4/NF-κB signaling pathwayInflammatory responseDiabetic cardiomyopa-thy
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