Zhang Jie, Qiu Hongmei, Huang Jiajun, Ding Shumei, Huang Bo, Wu Qin, Jiang Qingsong
Department of Pharmacology, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing, China.
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Guizhou, China.
Int J Exp Pathol. 2018 Dec;99(6):295-303. doi: 10.1111/iep.12296. Epub 2019 Jan 6.
The aim of this study was to establish a robust model of diabetic myocardial hypertrophy in Mus musculus castaneus mice. Mice were fed a high-fat diet for four weeks and then given streptozotocin (STZ, 40 mg kg d for 5 days, intraperitoneally) and fasting blood glucose (FBG) levels were tested after seven days. Mice with FBG levels above 11.1 mmol/L were considered diabetic. Diabetic mice continued to have access to the high-fat diet until cardiac hypertrophy developed. FBG and body weight (BW) were measured weekly. Myocardial hypertrophy was confirmed by left ventricle (LV) hypertrophy index (LVHI), LV/BW, LV histopathological observation and atrial natriuretic factor (ANF) mRNA expression. Serum insulin and plasma haemoglobin A1c (HbA1c) levels, total cholesterol (TCH) and triglyceride (TG) were measured, and then an insulin resistance index (HOMA.IR) was calculated. The level of FBG in the model group remained above 11.1 mmol/L, and the BW showed significant weight loss, compared with the control group (P < 0.01). The high levels of HbA1c, HOME.IR, TCH and TG, and the low level of insulin suggested that glucose metabolism was not balanced with insulin resistance; meanwhile, higher TCH and TG showed that dyslipidaemia had also developed. After the diabetic mice were kept on the high-energy diet for another four weeks, histopathological observation showed myocardial injuries, much more surface area and collagen fibres, higher LVHI and LV/BW, and elevated expression of ANF mRNA (P < 0.01), suggesting that myocardial hypertrophy had appeared in Mus musculus castaneus mice under the current experimental conditions. Thus a robust model of diabetic myocardial hypertrophy was established four weeks after confirmation of diabetes, which was induced by feeding a high-fat diet for four weeks combined with a repeated low-dose STZ exposure, in Mus musculus castaneus mice.
本研究的目的是在小家鼠中建立一个可靠的糖尿病性心肌肥大模型。小鼠先喂食高脂饮食四周,然后给予链脲佐菌素(STZ,40 mg/kg·d,腹腔注射,连续5天),7天后检测空腹血糖(FBG)水平。FBG水平高于11.1 mmol/L的小鼠被视为糖尿病小鼠。糖尿病小鼠继续给予高脂饮食,直至出现心脏肥大。每周测量FBG和体重(BW)。通过左心室(LV)肥大指数(LVHI)、LV/BW、LV组织病理学观察和心钠素(ANF)mRNA表达来确认心肌肥大。检测血清胰岛素和血浆糖化血红蛋白(HbA1c)水平、总胆固醇(TCH)和甘油三酯(TG),然后计算胰岛素抵抗指数(HOMA-IR)。与对照组相比,模型组的FBG水平维持在11.1 mmol/L以上,且BW显著减轻(P<0.01)。HbA1c、HOMA-IR、TCH和TG水平升高,胰岛素水平降低,提示糖代谢与胰岛素抵抗失衡;同时,TCH和TG升高表明血脂异常也已出现。糖尿病小鼠再给予高能饮食四周后,组织病理学观察显示心肌损伤、表面积和胶原纤维增多、LVHI和LV/BW升高以及ANF mRNA表达升高(P<0.01),表明在当前实验条件下小家鼠出现了心肌肥大。因此,在小家鼠中,通过四周高脂饮食喂养结合重复低剂量STZ暴露诱导糖尿病,在糖尿病确诊四周后建立了一个可靠的糖尿病性心肌肥大模型。