Objective:To investigate impacts of asperuloside on myocardial inflammatory injury in diabetes rats by regulating cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway.Methods:SD rats and rat cardiomyo-cytes H9C2 were randomly grouped into control group,model group,low-dose asperuloside group,high-dose asperuloside group,high-dose asperuloside+empty load group and high-dose asperuloside+cGAS overexpression group,except for control group,rats in each group were fed with high-fat diet for 8 weeks,and then intraperitoneal injection of streptozotocin was applied to construct the model of diabetes cardiomyopathy(DCM);in addition to control group,H9C2 cells in each group were induced by high glucose(25 mol/L glucose)to induce in vitro diabetes heart injury model,after grouping and processing,the cardiac function of rats in each group was measured by ultrasound,left ventricular ejection fraction(LVEF)and left ventricular short axis shortening rate(FS)were compared;the rat heart index was calculated;myocardial histopathological changes were observed by HE staining;TUNEL staining was applied to detect apoptosis in myocardial tissue of rats in each group;ELISA was applied to detect levels of inflammatory factors such as TNF-α and IL-18 in serum and myocardial tissue of rats in each group;EdU and TUNEL staining were applied to detect proliferation and apoptosis of H9C2 cells in each group;levels of TNF-α and IL-18 in H9C2 cells in each group were detected by ELISA;Western blot was applied to detect expressions of cGAS-STING pathway proteins in myocardial tissue and H9C2 cells of rats in each group.Results:Compared with control group,LVEF,FS and proliferation rate of H9C2 cells in model group were obviously decreased(P<0.05),while cardiac index,percentage of apoptosis in myocardial tissue,levels of TNF-α and IL-18 in serum and myocardial tissue,rate of apoptosis,and levels of TNF-α and IL-18 in H9C2 cells,and expressions of cGAS and STING proteins in myocardial tissue and H9C2 cells were obviously increased(P<0.05);compared with model group,LVEF,FS and proliferation rate of H9C2 cells in low-dose asperuloside group,high-dose asperuloside group,high-dose asperuloside+empty load group were obviously increased(P<0.05),while cardiac index,percentage of apoptosis in myocardial tissue,levels of TNF-α and IL-18 in serum and myocardial tissue,rate of apoptosis and levels of TNF-α and IL-18 in H9C2 cells,and expressions of cGAS and STING proteins in myocardial tissue and H9C2 cells were obviously decreased(P<0.05);compared with low-dose asperuloside group,LVEF,FS,and proliferation rate of H9C2 cells in high-dose asperuloside group,high-dose asperuloside+empty load group were obviously increased(P<0.05),while cardiac index,percentage of apoptosis in myocardial tissue,levels of TNF-α and IL-18 in serum and myocardial tissue,rate of apoptosis and levels of TNF-α and IL-18 in H9C2 cells,and expressions of cGAS and STING proteins in myocardial tissue and H9C2 cells were obviously decreased(P<0.05);compared with high-dose asperuloside group,LVEF,FS and proliferation rate of H9C2 cells in high-dose asperuloside+cGAS overexpression group were obviously decreased(P<0.05),while cardiac index,percentage of apoptosis in myocardial tissue,levels of TNF-α and IL-18 in serum and myocardial tissue,rate of apoptosis and levels of TNF-α and IL-18 in H9C2 cells,and expressions of cGAS and STING proteins in myocardial tissue and H9C2 cells were obviously increased(P<0.05),there was no significantly difference in various indicators of rats and H9C2 cells in high-dose asperuloside+empty load group(P>0.05).Conclusion:Asperuloside can inhibit inflammation via down-regulation of cGAS-STING pathway,thereby reducing myocardial inflammatory injury in diabetes rats,inhibiting apoptosis of myocardial cells induced by high glucose,and ultimately improving cardiac function in rats.

Objective:To investigate impacts of asperuloside on myocardial inflammatory injury in diabetes rats by regulating cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway.Methods:SD rats and rat cardiomyo-cytes H9C2 were randomly grouped into control group,model group,low-dose asperuloside group,high-dose asperuloside group,high-dose asperuloside+empty load group and high-dose asperuloside+cGAS overexpression group,except for control group,rats in each group were fed with high-fat diet for 8 weeks,and then intraperitoneal injection of streptozotocin was applied to construct the model of diabetes cardiomyopathy(DCM);in addition to control group,H9C2 cells in each group were induced by high glucose(25 mol/L glucose)to induce in vitro diabetes heart injury model,after grouping and processing,the cardiac function of rats in each group was measured by ultrasound,left ventricular ejection fraction(LVEF)and left ventricular short axis shortening rate(FS)were compared;the rat heart index was calculated;myocardial histopathological changes were observed by HE staining;TUNEL staining was applied to detect apoptosis in myocardial tissue of rats in each group;ELISA was applied to detect levels of inflammatory factors such as TNF-α and IL-18 in serum and myocardial tissue of rats in each group;EdU and TUNEL staining were applied to detect proliferation and apoptosis of H9C2 cells in each group;levels of TNF-α and IL-18 in H9C2 cells in each group were detected by ELISA;Western blot was applied to detect expressions of cGAS-STING pathway proteins in myocardial tissue and H9C2 cells of rats in each group.Results:Compared with control group,LVEF,FS and proliferation rate of H9C2 cells in model group were obviously decreased(P<0.05),while cardiac index,percentage of apoptosis in myocardial tissue,levels of TNF-α and IL-18 in serum and myocardial tissue,rate of apoptosis,and levels of TNF-α and IL-18 in H9C2 cells,and expressions of cGAS and STING proteins in myocardial tissue and H9C2 cells were obviously increased(P<0.05);compared with model group,LVEF,FS and proliferation rate of H9C2 cells in low-dose asperuloside group,high-dose asperuloside group,high-dose asperuloside+empty load group were obviously increased(P<0.05),while cardiac index,percentage of apoptosis in myocardial tissue,levels of TNF-α and IL-18 in serum and myocardial tissue,rate of apoptosis and levels of TNF-α and IL-18 in H9C2 cells,and expressions of cGAS and STING proteins in myocardial tissue and H9C2 cells were obviously decreased(P<0.05);compared with low-dose asperuloside group,LVEF,FS,and proliferation rate of H9C2 cells in high-dose asperuloside group,high-dose asperuloside+empty load group were obviously increased(P<0.05),while cardiac index,percentage of apoptosis in myocardial tissue,levels of TNF-α and IL-18 in serum and myocardial tissue,rate of apoptosis and levels of TNF-α and IL-18 in H9C2 cells,and expressions of cGAS and STING proteins in myocardial tissue and H9C2 cells were obviously decreased(P<0.05);compared with high-dose asperuloside group,LVEF,FS and proliferation rate of H9C2 cells in high-dose asperuloside+cGAS overexpression group were obviously decreased(P<0.05),while cardiac index,percentage of apoptosis in myocardial tissue,levels of TNF-α and IL-18 in serum and myocardial tissue,rate of apoptosis and levels of TNF-α and IL-18 in H9C2 cells,and expressions of cGAS and STING proteins in myocardial tissue and H9C2 cells were obviously increased(P<0.05),there was no significantly difference in various indicators of rats and H9C2 cells in high-dose asperuloside+empty load group(P>0.05).Conclusion:Asperuloside can inhibit inflammation via down-regulation of cGAS-STING pathway,thereby reducing myocardial inflammatory injury in diabetes rats,inhibiting apoptosis of myocardial cells induced by high glucose,and ultimately improving cardiac function in rats.