Telmisartan Improve Oxidative Stress In Kidney Of Insulin Resistant Rats

ObjectiveTo study the damage of oxidative stress to kidney and explore the protective effect of telmisartan on renal and provide an effective way to prevent chronic kidney disease in clinical.MethodsInsulin resistance rat models induced by high-fat diet and evaluated by euglycemic-hyperinsulinemic clamp technique.30 Wistar rats were divided into three groups randomly:①C group, contril diet;②IR group, high-fat diet;③T group, high-fat diet and received telmisartan. After six weeks of telmisartan, application of automatic biochemical analyzer detected the changes of lipids in blood; free fatty acid (FFA)was detected by colorimetry; the insulin level of blood plasma was detected by radiation immunization; microalbuminuria (MAU) was determined by the immunoturbidimetry; ultrastructural changes of kidney was observated in electron microscopic; the content of MDA in renal cortex was detected by thiobarbituric acid; the activity of SOD in renal cortex was detected by xanthine oxidase; the expressions of glomerular eNOS protein was detected by immunohistochemistry; NAD(P)H oxidase subunit p47phox and p22phox mRNA in renal cortex was measured by RT-PCR.Results(1) Compared with C group, Glucose infusion rate (GIR60-120) of IR significantly lower (7.03±0.99vs0.37±0.3, Pvalue<0.001), insulin sensitivity index(ISI) also lower (-3.92±0.14vs-4.89±0.41, Pvalue<0.001) and FFA(0.28±0.24vs0.56±0.30, P value<0.01), triglyceride(TG) (0.13±0.44 vs 1.53±0.27,Pvalue<0.001), total cholesterol (TC) (0.66±0.71vs0.52±0.81, Pvalue<0.001) significantly increased, descripting rat model of insulin resistance was successfully manufactured. Treatment by telmisartan, improving the state of IR:increased GIR60-12(0.37±0.38vs0.49±0.31, Pvalue<0.05) and ISI(-4.89±0.41vs-4.24±0.27, Pvalue<0.01); lower level of blood lipid: TG(1.53±0.27vs0.40±0.22, Pvalue<0.05), TC(0.66±0.71vs 1.11±0.92, Pvalue<0.05).(2) Compared with C group, microalbuminuria of IR significantly increased(0.39±0.17 vsl.79±0.67,Pvalue<0.05) and change of glomerular basement membrane thickening (0.18±0.03vs0.35±0.09μm, Pvalue<0.001) and some foot process fusion, lack of such could be seen in electron microscopy of IR. Treatment by telmisartan, reducing the formation of microalbuminuria(1.79±0.67vs0.62±0.24, Pvalue<0.05); improving the structure of the kidney:thickness of glomerular basement membrane (0.35±0.09vs 0.23±0.09μm, Pvalue<0.01), reducing absence and fusion of foot, protecting the kidney.(3) Compared with C group, the content of MDA in renal cortex of IR increased(1.71±0.09vs 3.60±0.11,Pvalue<0.01), the activity of SOD significantly lower(294±15.8vs 170±12.4, Pvalue<0.05) and expressions of eNOS protein (3.96±0.31vs 2.32±0.24, Pvalue<0.01) in the glomerular steped down markedly, NAD(P)H oxidase subunit p47phox and p22phox mRNA(0.65±0.056vs 1.33±0.05, Pvalue<0.01; 0.86±0.067vs 1.47±0.071, Pvalue<0.01) significantly higher. Treatment by telmisartan reducing damage of oxidative stress to the kidneys:lower the content of MDA(3.60±0.11vs 2.90±0.1, Pvalue<0.05), increased the activity of SOD (170±12.4vs 233±10.84,Pvalue<0.05), increased expression of eNOS protein(2.32±0.24vs 3.02±0.43, Pvalue<0.01), lower the level of NAD(P)H oxidase subunit p47phox and p22phox mRNA(1.33±0.057vs 0.98±0.065, Pvalue<0.01; 1.47±0.071vs 1.11±0.108 Pvalue<0.05). Concision(1) Kidney exists damage in the state of IR:including①ncreased excretion of microalbuminuria;②lomerular basement membrane thickening and some foot process fusion, lack of such.(2) Oxidative stress involved in kidney damage in the state of IR by NAD(P)H oxidase.(3) Telmisartan can improve the state of oxidative stress and reduce the damage of oxidative stress to kidney to protect the kidney.