吡格列酮对链脲佐菌素诱导糖尿病大鼠视网膜早期病变保护作用的研究

Effects of pioglitazone on MKP-1 and TSP-1 expression in early stages of diabetic retinopathy induced by streptozotocin

目的:探讨吡格列酮对链脲佐菌素诱导的糖尿病大鼠视网膜病变的影响及可能作用机制。方法:雄性SD大鼠30只,随机分为3组:正常对照组、糖尿病组和糖尿病吡格列酮治疗组。用链脲佐菌素腹腔注射建立糖尿病模型后,糖尿病吡格列酮治疗组给予吡格列酮灌胃(20 m g.kg-1.d-1),糖尿病组给予等量生理盐水,正常对照组给予等量自来水。每隔2周测量血糖1次。8周后取视网膜组织行免疫组织化学和RT-PCR检测TSP-1、MKP-1的变化。结果:成模8周时,糖尿病吡格列酮治疗组和糖尿病组血糖水平高于正常对照组,体重则低于正常对照组(P<0.01);在早期糖尿病组和糖尿病吡格列酮治疗组的大鼠视网膜各层中均有明显的TSP1和MKP-1表达,并以糖尿病吡格列酮治疗组为明显;糖尿病吡格列酮治疗组、糖尿病组和正常对照组TSP-1的荧光灰度值分别为513.2±16.8、461.4±32.4和382.7±18.7,MKP-1 mRNA的荧光灰度值分别为897.2±23.1、834.2±18.8和471.0±25.4,内参照GAPDH的荧光灰度值分别为868.4±13.2、857.4±26.8和846.7±23.2,各组间TSP-1和MKP-1 mRNA表达有显著性差异(P<0.01)。结论:吡格列酮可能通过TSP-1在一定程度上延缓糖尿病视网膜病变的发生,其作用机制可能涉及调节信号传导通路中MKP-1变化途径。

Objective： To explore the effects of piogilitazone on MKP-1 and TSP-1 expression in the early stages of diabetic retinopathy induced by streptozotocin （STZ） and the relevant mechanism in it. Methods ： Diabetic rats were induced by an intraperitoneal injection of STZ in SD rats. Thirty male SD rats were randomly divided into 3 groups ：diabetes adding pioglitazone group （intragastric administration pioglitazone 20 mg · kg^-1 · d^-1）, diabetes adding BBS group and normal control group. The body weight and blood glucose were measured every two weeks. Eight weeks later,all rats were killed and the expression of TSP-1 and MKP-1 mRNA was quantified in retinal tissue by immunohistochemistry and reverse transcription-polymerase chain reaction （RT- PCR） respectively. Results： TSP-1 and MKP-1 concentrations were significantly increased in the diabetic rats＇ retinal tissue compared to the control rats. Diabetes groups adding pioglitazone caused the upregulation of TSP-1 and MKP-1 expression in the retina among the three groups. Conclusion： Pioglitazone treatment can significantly attenuate the evolutionary in the early stages of experimental diabetic retinopathy. Further studies should address the possible involvement of TSP-1 and MKP-1 in the correlational pathophysiology between pioglitazone and diabetic retinopathy.