Effect of rosiglitazone on SREBP-1 and TGF-β1 expressions and accumulation of ECM in renal tubular cells of Wistar rats treated with high fat diet / 中国病理生理杂志

AIM: To study the effect of high fat diet on the expression of sterol regulatory element biding protein-1 (SREBP-1) and transforming growth factor β_1 (TGF-β_1) in renal tubular cells and rosiglitazone intervention. METHODS: Wistar rats were treated with high fat diet and rosiglitazone for 3 months. The serum glucose, serum insulin and serum triglyceride were detected. Oil Red O staining was used to observe the renal lipid deposit and Masson staining was for the detection of ECM accumulation. SREBP-1, TGF-β_1 and FN protein were determined by the methods of immunohistochemistry and Western blotting. SREBP-1 mRNA was detected by in situ hybridization. RESULTS: Rosiglitazone prevented effectively the increase in serum glucose, serum insulin and serum triglyceride resulted from high fat diet. High fat diet led to lipid droplet formation in renal tubular cells and interstitial ECM accumulation, which was decreased by rosiglitazone treatment. Compared to normal rats, SREBP-1 protein and SREBP-1 mRNA showed high expressions in high fat diet rats that were lowered by rosiglitazone. The precursor segment and mature segment of SREBP-1 protein were decreased by 27.39% and 27.32%. Similarly, the high expressions of TGF-β_1 and FN protein in kidney of high fat diet rats were also prevented by rosiglitazone intervention. Compared to high fat diet rats, the expression of TGF-β_1 in rosiglitazone treatment rats was lowered by 19.14%. CONCLUSION: Rosiglitazone prevents effectively the over-expression of SREBP-1 and TGF-β_1 in renal tubular cells, and decreases lipid accumulation and ECM production in rats fed with high fat diet.

Effects of simvastatin on vascular smooth muscle cells regulated by sterol regulatory element binding proteins / 上海第二医科大学学报

Objective To explore the biphasic effects of simvastatin on vascular smooth muscle cells (VSMCs), which were regulated by sterol regulatory element binding proteins(SREBPs).Methods ① Rat primary VSMCs were cultured,the effects of different concentrations of simvastatin on proliferation and migration of VSMCs were observed, and the expression of SREBP-1 and SREBP-2 mRNA on VSMCs was detected.② Rat models of atherosclerosis were established,and were divided into atherosclerotic injured group (n=6), low concentration simvastatin group (n=6) and high concentration simvastatin group (n=6). Besides, normal control group (sham operation group, n=8) was established. Intragastric group and high concentration simvastation group, respectively, while those in normal control group and atherosclerotic injured group were given same amount of normal saline. Rats were sacrificed 4 weeks later. Plasma lipid levels were examined by enzymic method, ratios of intima/(intima + tunics media) of thoracic aorta and left common carotid artery were determined, and the expression of SREBP-1 and SREBP-2 mRNA on blood vessels was detected by RT-PCR. Results Simvastatin didn't show biphasic effects on the proliferation and migration of VSMCs. Low concentration simvastatin didn't promote the proliferation and migration of VSMCs, while high concentration simvastatin showed inhibition effect on the proliferation and migration of VSMCs, which was dose-dependent and independent of lipid regulation effect by simvastatin. Simvastatin could activate the expression of SREBP-1 and SREBP-2 mRNA of VSMCs. Moreover, high concentration simvastatin could significantly activate the expression of SREBP-1 and SREBP-2 mRNA. Conclusion Simvastatin can inhibit the proliferation and migration of VSMCs by activating SREBPs.

Effects of simvastatin on vascular smooth muscle cells regulated by steroi regulatory element binding proteins / 上海第二医科大学学报

Objective To explore the biphasic effects of simvastatin on vascular smooth muscle cells(VSMCs),which were regulated by sterol regulatory element binding proteins(SREBPs).Methods①Rat primary VSMCs were cultured,the effects of different concentrations of simvastatin on proliferation and migration of VSMCs were observed,and the expression of SREBP-1 and SREBP-2 mRNA on VSMCs was detected.②Rat models of atherosclerosis were established,and were divided into atherosclerotic injured group(n =6),low concentration simvastatin group(n=6) and high concentration simvastatin group(n=6).Besides,normal control group(sham operation group,n=8) was established.Intragastric administration of simvastation of 0.5 mg?kg~(-1)?d~(-1) and 2.5 mg?kg~(-1)?d~(-1) was conducted in low concentration simvastatin group and high concentration simvastation group,respectively,while those in normal control group and atherosclerotic injured group were given same amount of normal saline.Rats were sacrificed 4 weeks later.Plasma lipid levels were examined by enzymic method,ratios of intima/(intima+tunica media) of thoracic aorta and left common carotid artery were determined,and the expression of SREBP-1 and SREBP-2 mRNA on blood vessels was detected by RT-PCR.Results Simvastatin didn't show biphasic effects on the proliferation and migration of VSMCs.Low concentration simvastatin didn't promote the proliferation and migration of VSMCs,while high concentration simvastatin showed inhibition effect on the proliferation and migration of VSMCs,which was dose-dependent and independent of lipid regulation effect by simvastatin. Simvastatin could activate the expression of SREBP-1 and SREBP-2 mRNA of VSMCs.Moreover,high concentration simvastatin could significantly activate the expression of SREBP-1 and SREBP-2 mRNA.Conclusion Simvastatin can inhibit the proliferation and migration of VSMCs by activating SREBPs.