Rong Li, Sun Shuo, Zhu Feiyu, Zhao Yi, Gao Qin, Zhang Heng, Tang Bi, Wang Hongju, Kang Pinfang
Department of Cardiology, First Affiliated Hospital of Bengbu Medical College, Bengbu 233030, China.
Department of Clinical Medicine, South Campus, Anhui Medical University, Hefei 230000, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2020 Jan 30;40(1):87-92. doi: 10.12122/j.issn.1673-4254.2020.01.14.
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.
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 of cholesterol (TC), triglyceride (TG), and fasting insulin (FINS) were measured after 8 weeks of feeding, and the insulin resistance index (IRI) and insulin sensitivity index (ISI) were calculated; Echocardiographic evaluation of cardiac structure and function was performed, and Western blotting and real-time fluorescent quantitative PCR (RT-qRCP) were used to detect the protein and mRNA expressions of NLRP1, ASC, and caspase 1 in the myocardial tissue.
Compared with the control rats, the rats in the HC group had significantly increased body weight (BW), serum levels of TG and TC, mRNA expressions of NLRP1 and caspase 1, and the protein expression of NLRP1 ( < 0.01) without significant changes in FINS, IRI, ISI, or cardiac ultrasound findings ( > 0.05) or in myocardial ASC and caspase 1 protein expressions or serum levels of IL-1β and IL-18 ( > 0.05). In the diabetic rats, TC, TG, and FBG levels increased and FINS, ISI decreased significantly ( < 0.01); the left ventricular end-diastolic diameter (LVID) and the left ventricular end-systolic diameter (LVSD) increased while the ejection fraction (LVEF), short axis shortening rate (FS), and E/A ratio all decreased. The expressions of NLRP1/ASC/caspase 1 pathway mRNA and NLRP1 and caspase 1 proteins also increased but myocardium ASC protein expression did not show significant changes in the diabetic rats ( > 0.05). IL-1β and IL-18 levels were also significantly higher in the diabetic rats than in the control group ( < 0.05). Compared with those in HC group, the diabetic rats showed significantly increased serum FBG and decreased FINS, ISI and BW ( < 0.01) with decreased LVSD, LVEF and E/A ratio and increased levels of NLRP1 and caspase 1 protein expressions and serum L-1β and IL-18 levels ( < 0.01).
Diabetes can cause abnormal changes in cardiac structure and functions and induce inflammatory response in the myocardium, which may be related to the activation of NLRP1/ASC/ caspase 1 inflammasomes.
观察高脂高糖饮食大鼠及糖尿病大鼠心肌组织中NLRP1炎性小体的表达，分析NLRP1炎性小体在糖尿病心肌病发病机制中的作用。
雄性SD大鼠分为正常对照组、高脂高糖饮食（HC）组和糖尿病组。通过腹腔注射链脲佐菌素（STZ；30 mg/kg）建立糖尿病大鼠模型。喂养8周后测定血清胆固醇（TC）、甘油三酯（TG）和空腹胰岛素（FINS）水平，并计算胰岛素抵抗指数（IRI）和胰岛素敏感指数（ISI）；进行超声心动图评估心脏结构和功能，采用蛋白质印迹法和实时荧光定量PCR（RT-qRCP）检测心肌组织中NLRP1、ASC和半胱天冬酶1的蛋白及mRNA表达。
与对照大鼠相比，HC组大鼠体重（BW）显著增加，血清TG和TC水平升高，NLRP1和半胱天冬酶1的mRNA表达以及NLRP1蛋白表达显著增加（P<0.01），而FINS、IRI、ISI或心脏超声检查结果无显著变化（P>0.05），心肌ASC和半胱天冬酶1蛋白表达或血清IL-1β和IL-18水平也无显著变化（P>0.05）。糖尿病大鼠的TC、TG和空腹血糖（FBG）水平升高，FINS、ISI显著降低（P<0.01）；左心室舒张末期内径（LVID）和左心室收缩末期内径（LVSD）增加，而射血分数（LVEF）、短轴缩短率（FS）和E/A比值均降低。NLRP1/ASC/半胱天冬酶1通路mRNA以及NLRP1和半胱天冬酶1蛋白的表达也增加，但糖尿病大鼠心肌ASC蛋白表达无显著变化（P>0.05）。糖尿病大鼠的IL-1β和IL-18水平也显著高于对照组（P<0.05）。与HC组相比，糖尿病大鼠血清FBG显著升高，FINS、ISI和BW降低（P<0.01），LVSD、LVEF和E/A比值降低，NLRP1和半胱天冬酶1蛋白表达水平以及血清L-1β和IL-18水平升高（P<0.01）。
糖尿病可导致心脏结构和功能异常改变，诱发心肌炎症反应，这可能与NLRP1/ASC/半胱天冬酶1炎性小体的激活有关。
