NLRP1炎症体在糖尿病大鼠心肌组织内的表达

目的 观察高脂高糖饮食和糖尿病分组中核苷酸结合寡聚化结构域样受体1（NLRP1）炎症体在心肌组织中表达的情况，分析其在糖尿病心肌病中潜在的致病机制。方法 将实验大鼠分为3组：正常组、高糖高脂饮食组和糖尿病组。以链脲佐菌素（STZ）30 mg/kg腹腔注射复制糖尿病大鼠模型，造模成功8周后行血清学检测各组大鼠血清胆固醇、甘油三酯、空腹血糖及空腹胰岛素，并计算得出胰岛素抵抗指数（IRI）和胰岛素敏感性指数（ISI）；心脏彩超评估心脏结构及功能；免疫印迹法和实时荧光定量PCR检测心肌组织NLRP1、ASC和caspase 1的蛋白及mRNA表达等情况。结果 与正常组相比，高糖高脂饮食组体质量、血清胆固醇、甘油三酯增高，NLRP1 mRNA、caspase 1 mRNA及NLRP1蛋白表达增加(P<0.01)，但空腹胰岛素、IRI、ISI、心脏彩超未见明显变化（P>0.05），心肌组织ASC和caspase 1蛋白及血清IL-1β、IL-18水平无明显变化（P>0.05），而糖尿病组中，大鼠血清胆固醇、甘油三酯、空腹血糖升高，空腹胰岛素、ISI和体质量降低（P<0.01），左室舒张末期内径、左心室收缩末期内径增大，射血分数、短轴缩短率及E/A比值下降并伴有NLRP1/ASC/caspase 1通路mRNA同步增加和NLRP1、caspase 1蛋白水平升高，但心肌组织中ASC蛋白表达无明显升高（P>0.05）。此外糖尿病组中IL-1β、IL-18也较正常组升高（P<0.05）；与高糖高脂饮食相比糖尿病组大鼠空腹血糖升高伴有空腹胰岛素，ISI和体质量降低（P<0.01），心脏彩超提示左心室收缩末期内径，射血分数及E/A比值下降并伴有NLRP1、caspase 1蛋白表达增加和血清L-1β、IL-18升高（P<0.01）。结论 糖尿病可诱发心脏结构和功能异常及心肌炎症反应，其机制可能与NLRP1/ASC/caspase 1炎症体活化有关。

Expression of NLRP1 inflammasomes in myocardial tissue of diabetic rats

Objective To observe the expression of NLRP1 inflammasomes in myocardial tissues in rats with a high-fat and highsugar diet and in diabetic rats analyze the role of NLRP1 inflammasomes in the pathogenesis of diabetic cardiomyopathy.Methods Male SD rats were divided into normal control group, high-sugar and high-fat diet (HC) group and diabetes group.Rat models of diabetes were established by intraperitoneal injection of streptozotocin (STZ; 30 mg/kg). Serum levels ofcholesterol (TC), triglyceride (TG), and fasting insulin (FINS) were measured after 8 weeks of feeding, and the insulinresistance index (IRI) and insulin sensitivity index (ISI) were calculated; Echocardiographic evaluation of cardiac structure andfunction was performed, and Western blotting and real-time fluorescent quantitative PCR (RT-qRCP) were used to detect theprotein and mRNA expressions of NLRP1, ASC, and caspase 1 in the myocardial tissue. Results Compared with the controlrats, the rats in the HC group had significantly increased body weight (BW), serum levels of TG and TC, mRNA expressions ofNLRP1 and caspase 1, and the protein expression of NLRP1 (P<0.01) without significant changes in FINS, IRI, ISI, or cardiacultrasound findings (P>0.05) or in myocardial ASC and caspase 1 protein expressions or serum levels of IL-1β and IL-18(P>0.05). In the diabetic rats, TC, TG, and FBG levels increased and FINS, ISI decreased significantly (P<0.01); the leftventricular end-diastolic diameter (LVID) and the left ventricular end-systolic diameter (LVSD) increased while the ejectionfraction (LVEF), short axis shortening rate (FS), and E/A ratio all decreased. The expressions of NLRP1/ASC/caspase 1 pathwaymRNA and NLRP1 and caspase 1 proteins also increased but myocardium ASC protein expression did not show significantchanges in the diabetic rats (P>0.05). IL-1β and IL-18 levels were also significantly higher in the diabetic rats than in the controlgroup (P<0.05). Compared with those in HC group, the diabetic rats showed significantly increased serum FBG and decreasedFINS, ISI and BW (P<0.01) with decreased LVSD, LVEF and E/A ratio and increased levels of NLRP1 and caspase 1 proteinexpressions and serum L-1β and IL-18 levels (P<0.01). Conclusion Diabetes can cause abnormal changes in cardiac structureand functions and induce inflammatory response in the myocardium, which may be related to the activation of NLRP1/ASC/caspase 1 inflammasomes.