辣椒辣素对糖尿病大鼠模型视网膜血管通透性的影响

The effect of capsaicin on the retinal vascular permeability in diabetic rats

目的 探讨辣椒辣素对糖尿病大鼠(DM)视网膜血管通透性及新生血管的影响。方法 选取8周龄雄性SD大鼠24只,随机分为4组(n=6):正常对照组(NC)、糖尿病组(DM)、糖尿病3 mg/kg辣椒辣素处理组(CAP3)、糖尿病6 mg/kg辣椒辣素处理组(CAP6)。3组糖尿病组大鼠均采用高脂饲料(HFD)+小剂量链脲佐菌素(STZ)联合诱导,建立2型糖尿病大鼠(T2DM)模型。监测4组大鼠体质量和空腹血糖。检测血清中总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)浓度;伊文思蓝造影观察视网膜血管通透性改变;免疫荧光检测视网膜辣椒辣素受体1(TRPV1)分布;Western blot检测视网膜TRPV1、血管内皮生长因子(VEGF)、闭锁蛋白(occludin)水平。结果 与DM组相比,生化指标提示CAP3、CAP6组大鼠血清中TC、TG、LDL浓度降低(P<0.01);造影结果提示DM组大鼠视网膜血管通透性增高,存在多处强荧光渗漏区域,CAP3、CAP6处理组渗漏减轻;免疫荧光显示,CAP3、CAP6组视网膜神经节细胞层、内核层及外核层TRPV1激活;蛋白检测提示视网膜TRPV1升高,VEGF表达下降、occludin表达上升(P<0.01)。结论 辣椒辣素具有改善糖尿病视网膜病变作用,其机制可能是通过激活视网膜TRPV1受体,降低VEGF、升高occludin的表达。

Objective To investigate the effect of capsaicin on retinal vascular permeability in diabetic rats(DM).Methods 24 eight-week-old male sprague-dawley(SD)rats were randomly categorized into four groups(n=6):control group(NC),diabetic group(DM),diabetic group with 3 mg/kg capsaicin treatment(CAP3)and diabetic group with 6 mg/kg capsaicin treatment(CAP6).Type 2 diabetic rat(T2DM)model was established by high-fat diet combined with small-dose streptozotocin(STZ)induction.The body weight and fasting blood glucose in 4 groups were monitored.Total cholesterol(TC),triglycerides(TG),low density lipoprotein(LDL),high density lipoprotein(HDL)concentrations in serum were detected according to manufacturer′s instructions.Evans blue angiography was used to observe the changes of retinal vascular permeability.Immunofluorescence was used to measure the distribution and expression of transient receptor potential vanillic 1(TRPV1)in retina.Western blot was used to detect the expression of TRPV1,vascular endothelial growth factor(VEGF)and occludin in rat retina.Results Compared with the DM group,serum total cholesterol(TC),triglyceride(TG)and low density lipoprotein(LDL)levels in the CAP3 and CAP6 groups significantly decreased(P<0.01).The results of angiography showed that the retinal vascular permeability increased in the DM group and that there were many strong fluorescent leakage areas,while the leakage was reduced in CAP3 and CAP6 groups.In CAP3 and CAP6 groups,immunofluorescence showed the activation of TRPV1 in the retinal ganglion cell layer,inner nuclear layer and outer nuclear layer.Western blot indicated that the expression of TRPV1 and occludin increased while the expression of VEGF decreased(P<0.01).Conclusion Capsaicin may exert the effect of improving diabetic retinopathy,underlying which the mechanism may be that capscicin activates retinal TRPV1,resulting in the downregulation of VEGF and upregulation of occuldin.