福辛普利联合非诺贝特对糖尿病小鼠视网膜病变干预作用的研究

The studying of fosinopril combined with fenofibrate on the preventing of diabetic retinopathy in diabetic mice

目的探讨福辛普利联合非诺贝特对糖尿病(DM)小鼠视网膜病变(DR)的治疗作用及机制。方法 ICR小鼠随机分为5组,每组30只:A组(假造模)、B组(DM模型)、C组[福辛普利干预,20 mg/(kg·d)]、D组[非诺贝特干预,400 mg/(kg·d)]、E组[福辛普利20 mg/(kg·d)+非诺贝特400 mg/(kg·d)干预]。RT-PCR法测定Bax与Bcl-2基因m RNA的表达水平。TUNEL染色法检测视网膜组织细胞凋亡情况。测定并比较各组谷胱甘肽过氧化物酶(GSH-PX)、超氧化物歧化酶(SOD)活性、丙二醛(MDA)、活性氧类物质(ROS)及血管内皮生长因子(VEGF)水平。结果 A组Bcl-2 m RNA、B组Bax m RNA水平高于其他4组;E组Bcl-2 m RNA水平高于C、D组,而Bax m RNA水平低于C、D组(均P<0.05)。B组TUNEL指数最高,E组<D组<C组<B组(均P<0.05),但E组与A组差异无统计学意义。B组GSH-PX、SOD活性均低于其他4组,而ROS、MDA、VEGF均高于其他4组;E组GSH-PX、SOD水平均高于C、D组,而ROS、MDA、VEGF均低于C、D组(均P<0.05)。结论福辛普利和非诺贝特均能通过抑制凋亡与抗氧化对DM小鼠视网膜起到一定的保护作用,两药联合应用效果更佳。

Objective To study the effect and mechanism of the Fosinopril combined with Fenofibrate on the prevent- ing of diabetic retinopathy. Methods A total of 150 viripotent ICR mice（100 male mice, 50 female mice） were randomly di- vided into five groups（n=30）, including A group （Sham group）, B group （Model group）, C group [Fosinopril prevented group, 20 mg/（kg·d）], D group [Fenofibrate prevented group, 400 mg/（kg· d）] and E group （Fosinopril combined with Fenofibrate pre- vented group）. The expression levels of Bax and Bel-2 gene mRNA were determined by RT-PCR method. TUNEL staining method was used to detect the apoptosisi of retinal cells. Results The Bcl-2 mRNA of A group, Bax mRNA of B group were higher than those of other four groups. Bcl-2 mRNA of E group was higher than that of C group and D group, while the Bax mRNA was lower than those of two groups （all P 〈 0.05）. The TUNEL index of B group was the highest than other groups, which of E group 〈 D group 〈 C group 〈B group （all P 〈 0.05 ）, and which of A and E groups were similar. The activi- ties of GSH-PX and SOD of B group were lower than those of other four groups, while the levels of ROS, MDA, VEGF were higher than those of them, the activity of GSH-PX and SOD of E group were higher than those of C and D groups, while the levels of ROS, MDA, VEGF were lower than them （all P 〈 0.05）. Conclusion Fosinopril and Fenofibrate can improve dia- betic retinopathy through inhibiting the apoptosis and antioxidation. The combination of them can get even better effect.