目的制备模拟人类发病过程的大鼠2型糖尿病心肌纤维化气虚痰瘀证模型。方法用雄性5周龄SD大鼠40只,随机分为正常对照组8只、高糖高脂组8只、模型组24只,高糖高脂喂养4周造成胰岛素抵抗后,正常对照组和高糖高脂对照组分组予以普食和高糖高脂饲料喂养。模型组于第5周予以腹腔注射2次1%小剂量STZ,2次之间间隔48 h,糖尿病造模成功后,随机继续高糖高脂喂养22周。通过心肌病理Masson染色、免疫组织化学染色测定CollagenⅠ、CollagenⅢ和β-actin,氯胺T法测定羟脯氨酸表达。结果模型组心肌病理切片及免疫组化结果显示存在心肌纤维化,正常组和高糖高脂组几乎没有;模型组TG、TC、LDL的值高于正常组;模型组和高糖高脂组胰岛素水平高于正常组;模型组脂联素水平低于正常组和高糖高脂组;模型组IL-1、TNF-α高于正常组和高糖高脂组;模型组羟脯氨酸、NTpro-BNP高于正常组和高糖高脂组。糖尿病大鼠在高糖高脂喂养8、12、16周,逐渐有血脂升高的趋势,开始出现高脂血症,NT-pro BNp和羟脯氨酸逐渐升高,但心肌Masson染色显示心肌纤维化不明显,20周的病理切片显示心肌纤维化开始明显,随着高糖高脂喂养时间越久糖尿病大鼠精神状态越差,饮食减少、体力活动量逐渐减少,趋向死亡的数量增加。结论造模成功后,大鼠的病理因素有痰和瘀,病位在脾和肾,证明2型糖尿病心肌纤维化气阴两虚、痰瘀互结证模型成立。
Objective: To establish Qi-asthenia and phlegm-stasis model in type 2 diabetic rats with myocardial fibrosis to imitate Pathogenesis of human. Methods: 40 5-week-old SD rats were randomly divided into the control group(n = 8),high-sugar and high-fat group(n = 8),and the model group(n = 24). High-sugar and high-fat group were fed for 4 weeks,causing insulin resistance. The control group and high-sugar and high-fat group were fed with normal food and high-sugar and high-fat food,respectively. In the fifth week,the model group received intraperitoneal injection with 1% low dose of STZ for twice,interval between two 48 h. After successful modeling of diabetes,they randomly continued to be fed with high-sugar and high-fat food for 22 weeks. Collagen I,Collagen III and α-actin were detected with Masson staining of Myocardial pathology and immunohistochemistry;Hydroxylproline was detected with Chloramine T method. Results: In the model group,the myocardial pathological sections and the results of immunohistochemistry showed that there was myocardial fibrosis,which,however,didn't exist in the control group and high-sugar and high-fat group. TG,TC and LDL in the model group was higher than that of the control group. The insulin level in the model group and high-sugar and high-fat group was higher than that of the control group;adiponectin level in the model group was lower than that of the control group and high-sugar and high-fat group;IL-1,TNF-α in the model group was higher than that of the control group and high-sugar and high-fat group,as well as Hydroxylproline and NTpro-BNP. Diabetic rats were fed with high glucose and high fat for 8 w,12 w,and 16 w. There is a trend of increasing blood lipids;hyperlipidemia began to appear;NT-pro BNp and Hydroxylproline gradually rose,but myocardial Masson staining showed no significant myocardial fibrosis. Pathological section in 20 th week showed significant myocardial fibrosis. The longer they were fed with high glucose and high fat,the worse the mental st