前列地尔对糖尿病大鼠视网膜Bcl-2、Bax表达的影响

Effect of alprostadil on the expression of Bax and Bcl-2 in retinal tissues of rats with diabetic mellitus

目的观察前列地尔对糖尿病大鼠视网膜组织细胞凋亡相关基因Bcl-2和Bax表达的影响,探讨前列地尔防治糖尿病性视网膜病变的作用机制。方法选择健康成年SD大鼠40只,随机分成正常对照组、模型组、前列地尔低剂量(0.5μg/kg)组和高剂量(1μg/kg)组。腹腔内注射链脲佐菌素(STZ)诱发大鼠糖尿病。前列地尔治疗组给予前列地尔静脉注射4周,模型组和对照组灌服等体积生理盐水,随后进行视网膜组织取材,采用Real Time PCR法检测Bcl-2和Bax的mRNA表达,采用Western Blot法检测Bcl-2和Bax的蛋白表达。结果 1)Bcl-2 mRNA和蛋白表达结果:模型组(0.42±0.05、0.33±0.03)均显著高于对照组(0.37±0.11、0.28±0.03)(P<0.05);前列地尔低剂量组(0.56±0.06、0.46±0.04)、高剂量组(0.65±0.04、0.59±0.04)均显著高于模型组(0.42±0.05、0.33±0.03),且与剂量呈正相关(P<0.05);2)Bax mRNA和蛋白表达结果:模型组(0.75±0.27、0.71±0.04)均显著高于对照组(0.33±0.05、0.22±0.03)(P<0.05);前列地尔低剂量组(0.60±0.08、0.48±0.04)、高剂量组(0.44±0.07、0.31±0.02)均显著低于模型组(0.75±0.27、0.71±0.04),且与剂量呈负相关(P<0.05)。结论前列地尔可通过调节糖尿病大鼠视网膜组织中Bax和Bcl-2的表达改善视网膜病变。

Objective To observe the effect of alprostadil on the expression of apoptosis-related genes, Bcl-2 and Bax in retinal tissues of diabetic rats, and to explore the mechanism of alprostadil for preventing and curing diabetic retinopathy. Methods Forty healthy adult SD rats were chosen and randomly divided into the control group, the model group, alprostadil low-dose group （0.5 ug/kg） and alprostadil high-dose group （1 ug/kg）. Diabetic mellitus was induced by intraperitoneal injection of streptozotocin （STZ）. The rats in alprostadil-treated groups had intravenous drip with alprostadil solution for 4 weeks, while those in the control group were given the same volume of saline by gavage. Retinal tissues of all the rats were sampled. Real-time polymerase chain reaction was used to detect the mRNA expression of Bcl-2 and Bax, and Western Blot assay to determine the protein expression of Bcl-2 and Bax. Results The expression levels of Bcl-2 mRNA and protein in retina in the model group were significantly higher than those of the control group （（0.42±0.05） vs. （0.37±0.11）, （0.33±0.03） vs. （0.28±0.03）, （P〈0.05））. The expression levels of Bcl-2 mRNA and protein in retina in alprostadil low-dose group （（0.56±0.06）, （0.46±0.04）） and alprostadil high-dose group （（0.65±0.04）, （0.59±0.04）） were significantly higher than those of the model group （（0.42±0.05）, （0.33±0.03））, and shown a positive correlation with the dose of alprostadil （P〈0.05）. The expression levels of Bax mRNA and protein in retina in the model group were significantly higher than those of the control group （（0.75±0.27） vs. （0.33±0.05）, （0.71±0.04） vs. （0.22±0.03）, （P〈0.05））. The expression levels of Bax mRNA and protein in retina in alprostadil low-dose group （（0.60±0.08）, （0.48±0.04）） and alprostadil high-dose group （（0.44±0.07）, （0.31±0.02）） were significantly lower than those of the model group （（0.75±0.27）, （0.71±0.04））, and shown a negative correlation with the dose of alprostadil （P〈0.05）. Conclusions Alprostadil may improve diabetic retinopathy by regulating the expression of Bcl-2 and Bax in retina tissues of diabetic rats.