Yang Zhang-Liang, Xu Hui-Lin, Cheng Yin, Zhao Jin-Guo, Zhou Yu-Jie, Weng Yang-Jing, Wang Xu-Tao, Qi Min-You
Institution of Pharmacology, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2018 Apr 8;34(4):309-312 339. doi: 10.12047/j.cjap.5638.2018.071.
To study the effect of ursolic acid on cardiomyopathy in mice with diabetes induced by high-fat diet combined with low dose streptozotocin, and to explore its possible mechanism.
Thirty male ICR mice were randomly divided into control group (=10) and moulding group (=20), the mice in the two groups were fed with regular diet and high-fat diet respectively for 6 weeks, and then the mice in the moulding group were injected with streptozotocin (30 mg/kg) for 5 successive days to induce diabetes mellitus (DM). Fasting blood glucose (FBG) was measured after 9 days. Mice with FBG over 11.1 mmol/L were regarded as DM. Twenty DM mice were randomly divided into model group and ursolic acid group (=10). Mice in each group were continuously administrated ursolic acid (100 mg/kg) or corresponding solvent intragastrically for 8 weeks. After that, FBG was measured, body weight (BW), heart weight and left ventricular weight were weighed in order to calculate the heart mass index (HMI) and left ventricular mass index (LVMI). Levels of creatine kinase (CK), lactate dehydrogenase (LDH) in serum and the level of superoxide dismutase (SOD), malondialdehyde (MDA) in myocardial tissue were detected. HE staining was used to observe pathological changes of myocardial tissue. Immunohistochemistry was employed to determine the expression of NOD-like receptor protein 3 (NLRP3) and interleukin 1β (IL-1β).
Compared with the control group, HMI, LVMI were apparently enlarged, levels of FBG, CK, LDH in serum and MDA in myocardial tissue were extremely increased, while the activity of SOD in myocardial tissue were extraordinary decreased in diabetic group. HE staining of myocardium showed that arrangement disorder of myocardial fibers, edema and hypertrophy in myocardial cell, as well as inflammatory cell infiltration in model group. Immunohistochemistry showed that the expression of NLRP3 and IL-1β in myocardial tissue increased obviously in model group, the above changes inursolic acid group were significantly ameliorated.
Ursolic acid has a obvious protective effect on myocardial injury in mice with diabetes induced by high-fat diet combined with low dose streptozotocin, and its mechanism may be associated with inhibiting NLRP3 inflammasome activation, reducing IL-1β generation and alleviating myocardial inflammatory injury.
研究熊果酸对高脂饮食联合低剂量链脲佐菌素诱导的糖尿病小鼠心肌病的影响，并探讨其可能机制。
将30只雄性ICR小鼠随机分为对照组（n = 10）和造模组（n = 20），两组小鼠分别给予常规饮食和高脂饮食6周，然后对造模组小鼠连续5天注射链脲佐菌素（30 mg/kg）诱导糖尿病（DM）。9天后测定空腹血糖（FBG）。FBG超过11.1 mmol/L的小鼠被视为DM。将20只DM小鼠随机分为模型组和熊果酸组（n = 10）。每组小鼠连续8周灌胃给予熊果酸（100 mg/kg）或相应溶剂。之后，测定FBG，称量体重（BW）、心脏重量和左心室重量，以计算心脏质量指数（HMI）和左心室质量指数（LVMI）。检测血清中肌酸激酶（CK）、乳酸脱氢酶（LDH）水平以及心肌组织中超氧化物歧化酶（SOD）、丙二醛（MDA）水平。采用HE染色观察心肌组织病理变化。采用免疫组织化学法检测NOD样受体蛋白3（NLRP3）和白细胞介素1β（IL-1β）的表达。
与对照组相比，糖尿病组HMI、LVMI明显增大，血清中FBG、CK、LDH水平以及心肌组织中MDA水平极度升高，而心肌组织中SOD活性异常降低。心肌HE染色显示模型组心肌纤维排列紊乱、心肌细胞水肿肥大以及炎性细胞浸润。免疫组织化学显示模型组心肌组织中NLRP3和IL-1β表达明显增加，熊果酸组上述变化明显改善。
熊果酸对高脂饮食联合低剂量链脲佐菌素诱导的糖尿病小鼠心肌损伤具有明显的保护作用，其机制可能与抑制NLRP3炎性小体激活、减少IL-1β生成以及减轻心肌炎性损伤有关。
