木犀草素减轻糖尿病小鼠心肌损伤及其机制

Effects of luteolin on myocardial injury and underlying mechanisms in diabetic mice

目的探讨木犀草素(Luteolin,LTL)对糖尿病小鼠心肌损伤影响及其可能调控机制。方法腹腔注射链脲霉素制备1型糖尿病小鼠模型,将雄性C57/BL6J小鼠分为3组(每组16只):对照组,糖尿病组,糖尿病+木犀草素组。糖尿病+木犀草素组给予LTL 50 mg/(kg·d)灌胃,对照组和糖尿病组给予50 g/L的羧甲基纤维素钠灌胃。药物治疗3月后,小鼠心脏超声检测心功能;Masson评估胶原容积分数(collagen volume fraction,CVF);Tunel法检测心肌细胞凋亡;Western blot检测Rho和ROCK2的表达。结果与对照组相比,糖尿病组各项心功能指标显著降低(P<0.05),CVF显著增高(P<0.05),小鼠心肌细胞凋亡显著增高(P<0.05),Rho和ROCK2的表达显著增加(P<0.05);与糖尿病组相比,糖尿病+木犀草素组各项心功能指标明显改善(P<0.05),CVF显著降低(P<0.05),小鼠心肌细胞凋亡显著降低(P<0.05),Rho和ROCK2的表达降低(P<0.05)。结论 LTL可能通过抑制RhoA/ROCK2信号通路减少糖尿病小鼠心肌细胞凋亡,从而减轻糖尿病心肌损伤。

AIM To explore the effects and mechanisms of luteolin on heart impairment in diabetic mice. METHODS Diabetes was induced by a single intraperitoneal of streptozotocin. Male C57/BL6J mice were randomly divided into three groups （n=16）： control, diabetes, diabetes＋luteolin. The diabetes＋luteolin group were given a dose of 50 mg/（kg·d） of luteolin, while the control and diabetes groups received 50 g/L sodium carboxymethyl cellulose gavage. For 3 months, echocardiography was employed to evaluate cardiac function. Collagen volume fraction （CVF） was measured by masson staining and apoptotic index was examined by Tunel. Western blot was used to determine the expression of Rho and ROCK2. RESULTS Compared with the control group, cardiac function attenuated significantly （P〈0.05）, with increased CVF （P〈0.05）. There was enhanced apoptotic index （P〈0.05） and expression of Rho and ROCK2 were upregulated （P〈0.05） when compared to the control group. Compared with those in the diabetes group, the cardiac function was significantly improved （P〈0.05） and CVF significantly diminished （P〈0.05）. There was a restored apoptotic index （P〈0.05）, and there was reduction of Rho and ROCK2 levels （P〈0.05） by treatment with luteolin in the diabetes＋luteolin group. CONCLUSION Luteolin significantly decreases the apoptotic index and protects against myocardial injury in diabetic mice, possibly by inhibiting activation of RhoA/ROCK2 signaling.