The Effects Of Glucose, Angiotensin Ⅱ With Different Concentration And Losartan On The Expression Of Monocyte Chemoattractant Protein-1 In Cultured Rats Glomerular Mesangial Cells In Vitro

Objective To investigate the effects of different concentrations of Angiotensinâ…¡(Angâ…¡), glueose and Losartan on the expression of monocyte chemoattractant protein-1 (MCP-1) mRNA and protein synthesis in rats glomerular mesangial cells(RGMCs) in Vitro in order to provide theoretic basisi for the prevention and treatment of diabetic nephropathy(DN).Methods (1) RGMCs, used as target cells, were divided into control group (5.6mmol/L, groupA), intermediate glucose group(17.5mmol/L, groupB) and high glucose group(30mmol/L, groupC). (2) RGMCswere cultured in the medium with high glucose(30mmol/L), in different concentrations of Angâ…¡(10-9,10-7,10-5mmol/L) , and were interfered by Losartan. At same time, control group(5.6mmol/L,groupC) was established. After 48h exprosure, the supernatants and RGMCs were collected. The level of MCP-1 in supernatants was determined by ELISA and MCP-1mRNA in mesangial cells was detected by RT-PCR.Results(1)The expressions of MCP-1mRNA were poor in group A, which in group B and C were obviously higher than those in groupA (all P<0.01),and in group C were further than those in groupB at same time(all P<0.01), except for 48h;(2)The levels of MCP-1 protein in the supernatant persistently increased in group B and C by comparing group A (all P<0.01), except for 12h at group B, and which in group C were obviously higher than those in groupB (all P<0.01).High glucose could significantly increase the expression of MCP-1 mRNA and protein synthesis in RGMCs compared to that in the control(P<0.01);(3)Angâ…¡significantly increased the expression of MCP-1 mRNA and protein synthesis in RGMCs(P<0.01), which was the strongest at 10-7mol/L, but attenuated at 10-5mol/L;(4)Losartan could significantly decrease the expression of MCP-1mRNA and protein synthesis which were stimulated by high glucose and Angâ…¡.Conclusion(1)The expression of MCP-1mRNA and protein synthesis in rats glomerular mesanglal cells can be induced by glucose in dose-and time-dependent manners in the certain range.(2)The expression of MCP-1 mRNA and protein synthesis in RMCs can be induced by Angâ…¡, and in dose dependent manners in the certain range.(3) It can be significantly inhibited by Losartan that the elevated expression of MCP-1 mRNA and protein synthesis in RMCs which were stimulated by high glucose and Angâ…¡. It could be speculated that Losartan has a reno-protective effect via inhibiting inflammatory reaction beyond its effect on blood pressure.