目的 觀察柚皮苷對糖尿病大鼠心肌纖維化及信號傳導(dǎo)與轉(zhuǎn)錄激活因子3（STAT3）磷酸化水平的影響。方法 健康雄性SD大鼠ip鏈脲佐菌素（STZ）建立糖尿病模型，將模型成功大鼠隨機分為模型組和柚皮苷低、中、高（25、50、100 mg/kg）劑量組，另設(shè)正常大鼠為對照組，每天ig給藥1次，連續(xù)給藥8周，對照組和模型組給予等體積生理鹽水。8周后檢測大鼠空腹血糖；計算心臟指數(shù)；采用Masson染色觀察心肌纖維化程度；實時熒光定量PCR（qRT-PCR）法檢測大鼠心肌組織I型膠原（Collagen I）和纖連蛋白（FN）mRNA表達；免疫組化法檢測大鼠心肌組織Collagen I和FN蛋白表達；蛋白免疫印跡法（Western blotting）檢測大鼠心肌組織STAT3及其磷酸化STAT3（p-STAT3）的表達水平。結(jié)果 與對照組比較，模型組大鼠空腹血糖、心臟指數(shù)、心肌纖維化程度以及Collagen I、FN和p-STAT3表達均明顯升高（P < 0.05、0.01）；與模型組比較，柚皮苷高、中劑量組心臟指數(shù)、心肌纖維化程度以及Collagen I、FN和p-STAT3表達均明顯下降（P < 0.05、0.01）。結(jié)論 柚皮苷通過下調(diào)糖尿病大鼠心肌組織STAT3通路，減少心肌間質(zhì)中Collagen I和FN合成及沉積，從而改善糖尿病心肌病大鼠心肌纖維化。

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.

國家自然科學(xué)基金資助項目（81573216），牡丹江醫(yī)學(xué)院研究生創(chuàng)新科研項目（2016YJSCX-23MY、2017YJSCX-22MY），黑龍江省大學(xué)生創(chuàng)新創(chuàng)業(yè)訓(xùn)練計劃項目（201710229023）