Effects of liraglutide on the transforming growth factor-β1/Smads signaling pathway in renal tissues of elderly type 2 diabetic rats / 中华老年医学杂志

ABSTRACT

Objective:To examine the effects of liraglutide on the transforming growth factor-β1(TGF-β1)/Smads signaling pathway in renal tissues of elderly rats with type 2 diabetes mellitus(T2DM)and to explore the underlying mechanisms.Methods:A total of 75 healthy elderly male Sprague-Dawley rats aged 20 months and weighing(500±100)g were divided into the normal control group(Group N, n=25)and the model group( n=50)by using a random number table.Rats in the model group were given high-glucose and high-fat diets for 8 weeks and then were injected with a single dose(30 mg/kg)of 1% streptozotocin into the abdominal cavity.Forty-eight rats in the model group were successfully molded and were divided into the T2DM group(Group D, n=24)and the intervention group(Group LD, n=24). Rats in Group LD were abdominally injected with liraglutide in a dose of 200 μg·kg -1·d -1, and the other two groups were given an equal volume of saline.At the end of 4, 8 and 12 weeks, eight rats in each group were randomly selected and 24-hour urine collections were made to measure 24-hour urinary protein.Then the rats were anesthetized, blood samples were collected for biochemical tests, and renal tissues were removed for microscopic examination of pathological changes after HE staining.The expression of type Ⅳ collagen(Col-Ⅳ)was detected by using an immunohistochemical method, and the mRNA expression of TGF-β1, Smad3 and Smad7 was detected by using real-time fluorescence quantitative polymerase chain reaction.One-way analysis of variance was used for comparisons between the groups, and the LSD-t test was used for pairwise comparisons. Results:Compared with Group N, Group D showed thickening of the glomerular basement membrane, mesangial proliferation and interstitial fibrosis at each time-point, which grew worse with time, and the expression of TGF-β1 mRNA, Smad3 mRNA and Col-Ⅳ also increased significantly(12-week 0.69±0.01 vs.0.15±0.01, 0.51±0.02 vs.0.02±0.01, 183.33±2.08 vs.221.67±2.08, t=89.22, 60.87 and 24.52, P<0.05), while Smad7 mRNA levels decreased( t=13.42, P<0.05). Compared with Group D, the degree of renal fibrosis was reduced, and the expression of TGF-β1 mRNA, Smad3 mRNA and Col-Ⅳ at 12-week significantly decreased( t=71.703, 37.58 and 20.04, P<0.05), while Smad7 mRNA increased( t=9.96, P<0.05)in Group LD.With prolonged intervention of liraglutide, the lesions were mitigated, the expression of TGF-β1 mRNA, Smad3 mRNA and Col-Ⅳ decreased, and Smad7 mRNA increased gradually( P<0.05)in Group LD. Conclusions:Liraglutide has anti-renal fibrosis effects via inhibiting the TGF-β1/Smads pathway, thereby reducing the production of Col-Ⅳ, and can delay the progression of renal lesions in elderly T2DM rats.