In adipose tissue of rats on long-term high fat diet,the inflammatory changes the roles of angiotensin receptor blocker(ARB) in pimelitis and insulin resistance(IR) were observed.IR rat model was established by feeding high calorie and high fat diet.The change in insulin sensitivity was detected by euglycemic-hyperinsulinemic clamp technique 8 weeks after intervention by valsartan.The expression levels of CD68 and MCP-1 mRNA and proteins in adipose tissue were examined by RT-PCR and immunohistochemistry respectively.The parameters of blood glucose,insulin and blood lipid were analyzed.The results showed that in high fat diet group intra-abdominal obesity developed,the content of visceral fat and the number of inflammatory cells in local adipose tissue were significantly increased(P<0.01),the levels of serum triglyceride,free fatty acids and fasting serum insulin were markedly increased,the insulin sensitivity was significantly lowered(P<0.01),and the expression of CD68 and MCP-1 was significantly increased as compared with control group(P<0.01).In ARB interventional group,the content of visceral fat,the number of inflammatory cells and the expression of CD68 and MCP-1 in local adipose tissue were significantly reduced(all P<0.01),but the insulin sensitivity was significantly enhanced(P<0.01) as compared with high fat diet group.There were pimelitis and IR in rats with obesity induced by long-term high calorie and high fat diet.The ARB can significantly inhibit the infiltration of macrophages and the expression of MCP-1 in adipose tissue,thereby attenuating the inflammation and improving IR in rats.
The effects of synthetic Smac peptide(SmacN7) on chemotherapeutic sensitivity of bladder cancer cells were investigated.SmacN7 penetratin peptide was synthesized and delivered into T24 cells.MTT assay was used to evaluate the viability of T24 cells induced by low-dosage of MMC.Flow cytometry was used to analyze the proportions of apoptosis.Western blot was used to detect the expression of XIAP and Caspase-3.The activity of Caspase-3 was measured and the effect of SmacN7 combined with MMC on T24 cell lines was also determined.The results showed that SmacN7 penetratin peptide could successfully interact with endogenous XIAP,increase the proportions of apoptosis of T24 cell lines induced by low-dosage of MMC in a dose-and time-dependent manner.An obvious down-regulation of XIAP expression and up-regulation of Caspase-3 was identified by Western blot.The activity of Caspase-3 in experimental group was significantly increased as compared with that in the control group.As compared with MMC group,the viability of T24 cells in SmacN7 penetratin peptide+MMC group was markedly decreased to 2.22 and 3.61 folds at 24 h and 48 h respectively.It was concluded that SmacN7 penetratin peptide could act as a cell-permeable IAP inhibitor,inhibit the proliferation,induce apoptosis and enhance the chemosensitivity of bladder cancer cells to MMC.These findings indicate that SmacN7 penetratin peptide may be a very promising ageut for bladder cancer treatment when used in combination with chemotherapy.
