双丹明目胶囊对糖尿病视网膜病变大鼠血液流变学和视网膜微血管的影响

Effects of Shuangdan Mingmu capsules on blood rheology and retinal microvasculature in rats with diabetic retinopathy

目的探讨双丹明目胶囊对糖尿病视网膜病变(DR)大鼠血液流变学和视网膜微血管的影响。方法取SPF级雄性SD大鼠72只,将大鼠随机分为6组正常组、模型组、对照组、高剂量组、中剂量组和低剂量组,每组12只。正常组和模型组大鼠给予生理盐水,对照组大鼠给予羟苯磺酸钙(等效给药浓度为5.8 mg·kg^(-1)),高、中、低剂量组大鼠分别给予不同剂量的双丹明目胶囊(22.4 g·kg^(-1)、11.2 g·kg^(-1)、5.6 g·kg^(-1)),分别是临床等效剂量的2.0倍、1.0倍、0.5倍,各组均按10 mL·kg^(-1)剂量灌胃。每周观察大鼠一次,连续12周,检测或量化相关指标。血液流变学指标包括全血黏度(WBV)、血浆黏度(PV)、红细胞沉降率(ESR)、红细胞压积(HCT)、纤维蛋白原含量(FIB)。对各个时期SD大鼠眼底图片通过海德堡共聚焦激光造影仪自带软件进行分析,对大鼠眼底视网膜动脉、静脉血管管径和视网膜微血管荧光素渗漏面积进行量化。结果连续灌胃12周后,与模型组相比,对照组和高剂量组大鼠WBV、PV、ESR、HCT、FIB均降低(均为P<0.05),中剂量组HCT也降低(P<0.01);与高剂量组相比,低剂量组大鼠WBV、PV、ESR、HCT、FIB均升高,中剂量组大鼠除HCT外,各项指标亦均升高(均为P<0.01)。造模成功后,与正常组比较,其他各组大鼠视网膜动脉血管管径均变细,静脉血管管径均增粗(均为P<0.05)。干预12周后,高剂量组大鼠视网膜动脉血管管径接近正常组,静脉血管管径仍然变粗(均为P<0.05);其他各组大鼠视网膜动脉血管管径普遍变细,静脉血管管径迂曲扩张(均为P<0.05)。与模型组相比,对照组和高剂量组大鼠视网膜微血管荧光素渗漏面积减小(均为P<0.01);与对照组和高剂量组相比,中剂量组、低剂量组大鼠视网膜微血管荧光素渗漏面积均增大(均为P<0.01)。结论双丹明目胶囊可以改善DR大鼠血液流变学状态,扩张视网膜动脉,改善视网膜血供,减少视网膜微血管荧光素渗漏面积。

Objective To investigate the effects of Shuangdan Mingmu capsules on blood rheology and retinal microvasculature in rats with diabetic retinopathy(DR).Methods Totally 72 SPF-grade male SD rats were randomly divided into six groups normal group,model group,control group,high-dose group,medium-dose group,and low-dose group,with 12 rats in each group.The rats in the normal and model groups were given normal saline,the rats in the control group were given calcium dobesilate(equivalent drug concentration of 5.8 mg·kg^(-1)),and the rats in the high-,medium-and low-dose groups were given different doses of Shuangdan Mingmu capsules(22.4 g·kg^(-1),11.2 g·kg^(-1) and 5.6 g·kg^(-1)),which were 2.0,1.0 and 0.5 times of the clinical equivalent doses,respectively.All rats were fed with 10 mL·kg^(-1) volume by gavage.The rats were observed once a week for 12 weeks,and the relevant indexes were measured or quantified.Hemorheological indexes included whole blood viscosity(WBV),plasma viscosity(PV),erythrocyte sedimentation rate(ESR),hematocrit(HCT),and fibrinogen content(FIB).Fundus pictures of SD rats in each period were analyzed by Heidelberg Confocal Laser Angiograph self-contained software to quantify the fundus retinal arterial and venous vessel diameters and retinal microvascular fluorescein leakage area.Results After 12 weeks of continuous gavage,WBV,PV,ESR,HCT,and FIB were reduced in the control and high-dose groups compared with the model group(all P<0.05),and HCT was also reduced in the medium-dose group(P<0.01);compared with the high-dose group,WBV,PV,ESR,HCT,and FIB were increased in the low-dose group,and all indexes were increased in the medium-dose group except for HCT(all P<0.01).After successful modeling,compared with the normal group,the retinal arterial vascular diameters in other groups were thinner,and the venous vascular diameters were thicker(all P<0.05).After 12 weeks of intervention,the retinal arterial vascular diameters of rats in the high-dose group were close to those of rats in the normal group,while the venous vascular diameters were still thickened(all P<0.05);the retinal arterial vascular diameters of rats in the rest groups were thinner,and the venous vascular diameters were thicker(all P<0.05).Compared with the model group,the area of retinal microvascular fluorescein leakage in the control and high-dose groups decreased(all P<0.01);compared with the control and high-dose groups,the area of retinal microvascular fluorescein leakage in the medium-and low-dose groups increased(all P<0.01).Conclusion Shuangdan Mingmu capsules can improve the blood rheological status of DR rats,dilate retinal arteries,improve retinal blood supply,and reduce the area of retinal microvascular fluorescein leakage.