Protective Effect Of Sequoyitol On Renal Injury In Type2Diabetic Rats And The Potential Mechanisms

Objective:To observe the protective effect of sequoyitol on renal injury in type2diabetic rats and explore its conceivable mechanisms.Methods:Type2diabetic rats model was established by intraperitoneal injection with a single dose of STZ (35mg·kg-1) and fed with a high-fat high-sucrose diet. The model rats were randomly divided into model group (distilled water5ml·kg-1·d-1), sequoyitol with high, medium and low dosages groups (50,25, and12.5mg·kg-1·d-1, respectively), and acarbose group (20mg·kg-1·d-1). In addition, the control group (distilled water5ml·kg-1·d-1) was established. All animals were given drugs or distilled water with successive intragastric administration for6weeks. Body weight was recorded for6weeks fortnightly interval with all animals. The oral glucose tolerance test (OGTT) was performed after6weeks, and the values of area under curve (AUC) were calculated. Left kidney and right kidney were weighed and kidney weight index was calculated respectively. Levels of serum creatinine (Scr), blood urea nitrogen (BUN), total-antioxidative activity (T-AOC) and hydrogen peroxide (H2O2) in serum or kidney were measured. Levels of tumor necrosis factor-a (TNF-α) and interleukin-6(IL-6) in kidney were determined by ELISA. The primary pathologic changes and collagen deposition of kidney were observed by HE or Masson staining. The expression of TGF-β1positive cells in kidney were measured by immunohistochemistry. The expression of collagen Ⅰ, collagen Ⅲ, TNF-α, TGF-β1, p22phox and p47phox mRNA in kidney were performed by real time PCR. Protein expression of TGF-β1,p22phox and p47phox in kidney were detected by western blot.Results:①Compared with control group, body weight was significantly decreased in model group, while that of rats in all drug-treated groups didn’t continuously decrease.②The values of area under the curve were markedly increased in model group, and that of rats in sequoyitol with high-dose group was decreased.③The kidney weight index was markedly increased in model group, and that in all drug-treated groups were lower than model group.④The levels of Scr and BUN were significantly increased in model group, whereas those in all drug-treated groups were notably decreased.⑤Messangial matrix and basement membrane of glomerular were proliferated, and collagen deposition was appeared in the renal interstitium in model group, while treatment of sequoyitol could ameliorate these pathological damages.⑥The mRNA expressions of TNF-α and the levels of TNF-α, IL-6in kidney were notably increased in model group, while the mRNA expressions of TNF-α and the levels of TNF-α, IL-6were markedly decreased in sequoyitol groups.⑦The mRNA and protein expressions of p22phox and p47phox, and level of H2O2in kidney were significantly increased, while level of T-AOC was markedly decreased in model group. However, the mRNA and protein expressions of p22phox and p47phox, and level of H2O2were markedly decreased, while level of T-AOC was increased in sequoyitol groups.⑧The mRNA expressions of collagen Ⅰ and collagen Ⅲ in kidney were significantly increased in model group, while the mRNA expressions of collagen Ⅰ and collagen Ⅲ were markedly decreased in sequoyitol groups.⑨The mRNA or protein and positive cells expressions of TGF-β1in kidney were significantly up-regulated in model group, while the mRNA or protein and positive cells expressions of TGF-β1were markedly down-regulated in sequoyitol groups.Conclusion:Sequoyitol has protective effect on renal injury in type2diabetic rats. Its possible mechanisms are related with anti-oxidization, down-regulating the expressions of TGF-β1,TNF-a and IL-6.