目的 观察柚皮苷对糖尿病大鼠心肌纤维化及信号传导与转录激活因子3（STAT3）磷酸化水平的影响。方法 健康雄性SD大鼠ip链脲佐菌素（STZ）建立糖尿病模型，将模型成功大鼠随机分为模型组和柚皮苷低、中、高（25、50、100 mg/kg）剂量组，另设正常大鼠为对照组，每天ig给药1次，连续给药8周，对照组和模型组给予等体积生理盐水。8周后检测大鼠空腹血糖；计算心脏指数；采用Masson染色观察心肌纤维化程度；实时荧光定量PCR（qRT-PCR）法检测大鼠心肌组织I型胶原（Collagen I）和纤连蛋白（FN）mRNA表达；免疫组化法检测大鼠心肌组织Collagen I和FN蛋白表达；蛋白免疫印迹法（Western blotting）检测大鼠心肌组织STAT3及其磷酸化STAT3（p-STAT3）的表达水平。结果 与对照组比较，模型组大鼠空腹血糖、心脏指数、心肌纤维化程度以及Collagen I、FN和p-STAT3表达均明显升高（P < 0.05、0.01）；与模型组比较，柚皮苷高、中剂量组心脏指数、心肌纤维化程度以及Collagen I、FN和p-STAT3表达均明显下降（P < 0.05、0.01）。结论 柚皮苷通过下调糖尿病大鼠心肌组织STAT3通路，减少心肌间质中Collagen I和FN合成及沉积，从而改善糖尿病心肌病大鼠心肌纤维化。

Objective To observe the effects of naringin on interstitial fibrosis, signal transducer and activator of transcription (STAT3) phosphorylation in diabetic rats. Methods The male SD rats were administrated with streptozotocin (STZ) by ip to establish diabetic rat model, and then randomly divide into model group, naringin low, middle and high dose (25, 50, and 100 mg/kg) group. The normal rats injected with vehicle were designed as control group. Rats in each group were given the corresponding medicine by ig, once a day for eight weeks, while the normal group and the model group were orally administered with saline. At the end of the 8th week in treatment, fasting plasma glucose and heart mass index were measured. Masson staining was used to observe the myocardial fibrosis. qRT-PCR was used to detect the mRNA levels of collagen I and fibronetion (FN). Immunohistochemical method was performed to detect the depositions of collagen I and FN. Western blotting method was used to detect STAT3 and phosphorylation of STAT3. Results Compared with control group, fasting plasma glucose, heart mass index, the degree of myocardial fibrosis, and the expressions of collagen I and FN in left ventricular myocardial tissue of model group were significantly increased (P < 0.05 and 0.01). Compared with model group, fasting plasma glucose, heart mass index, the degree of myocardial fibrosis, and the expressions of collagen I and FN in left ventricular myocardial tissue of naringin middle and high dose group were significantly decreased. Conclusion Naringin retards the process of myocardial fibrosis in diabetic rats by downregulating the expression of STAT3, reducing the synthesis and depositions of collagen I and FN.

国家自然科学基金资助项目（81573216），牡丹江医学院研究生创新科研项目（2016YJSCX-23MY、2017YJSCX-22MY），黑龙江省大学生创新创业训练计划项目（201710229023）