Naringenin ameliorates myocardial remodeling by inhibiting NLRP3 inflammasome activation in diabetic mice

Abstract:

Objective：To study the effects of NAR on myocardial remodeling as well as its effects on NLRP3 inflammasome in dia－betic mice. Methods：Male C57BL/6 mice（n=35） were randomly divided into normal group（N group，n=7） and experimental group （n=28）. The mice in the experimental group were injected with STZ for 3 days to induce diabetes mellitus. Random blood glucose was measured after 7 days. Mice with random blood glucose over 16.7 mmol/L were regarded as diabetes mellitus. Finally，all the twenty-eight mice in the experimental group were successfully modeled. Twenty-eight diabetes mice were randomly divided into diabetes group（DM group），diabetes+low dose of NAR group（DM+LN group），diabetes+ middle dose of NAR group（DM+MN group），and dia－betes+high dose of NAR group（DM+HN group）. The mice in treatment group received different doses of NAR through intraperitoneal injection for 8 weeks. At the end of the study，the mice were sacrificed to observe the effects of NAR at different dose on the body weight and blood glucose. HE staining was used observe pathological changes of myocardial tissue. The myocardial CVF was calculated by Masson staining. Apoptosis was detected by TUNEL fluorescent staining. Western blot was applied to deter－mine the protein levels of NLRP3，ASC，Caspase-1，IL-1β，type Ⅰ collagen，and FN. PCR was used to analyze mRNA of NLRP3，ASC，Caspase-1，and IL-1β. Results：Masson staining showed that the CVF was significantly higher in DM group[（37.68±1.14）%] than in DM+LN group[（13.58±0.86）%]，DM+MN group[（9.50±0.59）%] and DM+HN group[（6.38±1.41）%]（P=0.000）. TUNEL fluorescent staining showed that cell apoptotic rate was significantly higher in DM group[（64.94±5.25）%] than in DM+LN group[（48.80±6.11）%]，DM+MN group[（31.85±4.44）%] and DM+HN group[（13.64±1.79）%]（P=0.000）. Western blot results demonstrated that the DM group（0.52±0.03） had significantly higher expression of NLRP3 compared with the DM+LN group（0.33±0.07），DM+MN group（0.23±0.06） and DM+HN group（0.15±0.04）（P=0.000）. Moreover，the DM group（0.69±0.09） had significantly higher expression of IL-1β than the DM+LN group（0.42±0.09），DM+MN group（0.25±0.04） and DM+HN group（0.09±0.03）（P=0.000）. Conclusion：NAR significantly attenuates the myocardial fibrosis and apoptosis in the diabetic mice，and its mechanism may be associated with inhibiting NLRP3 inflammasome activation，reducing the level of inflammation.