Role Of Resveratrol In The Colonic Smooth Muscle Motility And Cell Proliferation

Diabetes is a global disease,which has serious impact on human health.Diabetes has been characterized by elevated blood glucose and insufficiency of insulin,accompanied by certain chronic symptoms in many organs and tissues.Complications in the digestive system showing different degree of functional disorder and pathological changes are very common in diabetic patients,in which chronic transit constipation is the main complain.In the previous study of diabetic animal model,we found that the diabetic mice had constipation of slow transit of colon.This is related to the hyperproliferation and hyperfunction of PDGFRα⁺cells in colon.Resveratrol（Res）is a natural compound with many biological effects such as anti-oxidative stress,anti-inflammation and anti-obesity.The antidiabetic properties of Res have been extensively studied in animal models in the past decade.Previous studies have shown that Res can alleviate various symptoms caused by diabetes,such as lowering blood glucose level,relieving skeletal muscle disorder and liver dysfunction.In addition,Res has the biological function of promoting apoptosis and inhibiting cell proliferation.The present study investigated the effects of Res on colonic motility and cell proliferation.The results showed that Res can relax the colonic smooth muscle by inhibiting the L-type calcium channels and the RhoA/ROCK pathway related proteins.To study the effect of Res on the high-induced proliferation of cells.Therefore,the high glucose cultured NIH/3T3 cells was used to simulate PDGFRα⁺cells in the colon.The results showed that Res can inhibit the proliferation and promote the apoptosis of high glucose-cultured NIH/3T3 cells;After incubation with Res,the expression of Bax and NF-κB in the cytoplasm were up-regulated,but the expression of Bcl-2 and NF-κB protein in the nucleus were down-regulated.Finally,the effect of Res on CT26 cells was discussed.The results showed that Res can inhibit the proliferation and promote the apoptosis of colon cancer cell CT26;The expression levels of PTEN,Bax and NF-κB in the cytoplasm were up-regulated,but the expression levels of p-Akt,Bcl-2 and NF-κB protein in the nucleus were down-regulated after incubation with Res.The above results suggest that the Res can relax the colonic smooth muscle via Ca²⁺-dependent and Ca²⁺-independent pathway;Res can inhibit the proliferation of high glucose cultured-NIH/3T3 cells and CT26cells;The effect of Res may be related to the expression levels of Bax,Bcl-2,NF-κB,PTEN and p-Akt proteins in cells.