| 8-Epi prostaglandin F2 alpha (8-epi PGF2aipha) is one of a series of epi- prostaglandin(epi PGs), which is produced in vivo directly by free radical-catalyzed lipid peroxidation and independently of the cyclo-oxygenase pathway since 1990. Increase of superoxide production in various pathology and physiology may be involved in the development and the pathogenesis of diabetic nephropathy. And yet , its pathogenesis has not been elucidated fully because of lacking a specific index of in vivo lipid peroxidation. On the other hand, renin-angiotensin system (RAS) shows a high activity in diabetes. It can increase the extent of high perfusion, high pressure and high filtration of glomerular in diabetes, cause the dynamic changes of the circulatory system, stimulate proliferation of the extracellular matrix(ECM) in mesangium region and lead ultimately to glomerulosclerosis. Recent researches have proven that angiotensin converting enzyme inhibitors (ACEI) can lessen the renal injury in diabetes by decreasing the level of Ang â…¡ . However, active Ang â…¡ can be produced in other ways, and ACEI can induce obstinate cough in some patients, In this case the application of ACEI in clinic is limited. Ang â…¡ receptor antagonist has recently been produced, which can competitively inhibit the binding of Ang â…¡ to its receptor, and inhibit directly the activity of Ang â…¡ . But its effects on diabetic nephropathy is unclean The aim of , using a established radioimmunoassay method of 8- epi-PGF2a , is to observe the effects of angiotensin â…¡ type 1 receptor antagonist (ATIRA) -Valsartan on the kidney of diabetic rat and investigate the mechanism of diabetic nephropathy affected by valsartan in measuring the level of 8-epi PGF2 alpha and Ang â…¡ in serum.Methods: 8-epi PGF2 alpha was conjugated to HAS, and the conjugate was subcutaneously injected into rabbits to produce theantibody, 8-epi PGF2 alpha was linked to Na'25I to prepare the tracer 125I-8-epi PGF2 alpha. The level of 8-epi PGF2 alpha in plasma on the diabetic rats was determined by radioimmunoassay. Diabetic models were made by the streptozotocin (60mg/kg) intraperitoineal injection in thirty-two male SD rats. The rats which was successfully modeled were random divided into two groups. Group A: diabetic group(n=ll). Group B: diabetic therapeutic group(n=12). Valsartan (24mg/kg)was administered by gavage for 8 weeks. Group C: normal control group (n=8). Normal saline(3ml/d)was administered by gavage in group A and C. The blood pressure and 24-hour urinary protein excretions in the 4th and 8th week of the experiment were measured, and the levels of serum glucose(SG), serum creatinine (Scr), blood urea nitrogen(BUN), plasma Ang â…¡, whole blood and plasma superoxide dismutase(SOD), whole blood glutathione peroxidase(GSH-PX), plasma lipid peroxide(LPO), plasma malondialdehyde (MDA), plasma 8-epi PGF2 alpha in the 8th week of the experiment were also measured.Results: (1) The best antiserum used for radioimmunoassay was obtained after the 5th booster, presenting a high litres (1/24,000). The measurement range of the method was 6.25-800pg/ml, Sensitivity was 4.50pg/ml, intra- and inter-batch variation coefficients were 3.9% and 8.6% respectively. The cross reactivities with other PGs and the related metabolites were negligible. (2) The SG of group A and B was significantly higher than that in group C. There was no significant difference between the SG of group A and B (p > 0.05). (3) 24-hour urinary protein excretion in group A and B in the 4th and 8th week was significantly higher than that in group C. But the excretion in group B (21.6+4.2, 26.9+5.1 mg/24h) was significantly lower than that in group A (29.5+4.7 , 35.1+8.7mg)(p<0.01). (4) Scr, BUN: There was significant difference between group A (161.29+ 19.44p mol/1, 14.17 + 2.25mmol/l) and group B (111.48+ 18. 55u mol/1, 10.38+1.79mmol/l)( p<0.01). (5)The mean artery pressure: In the 4th and 8th week, the pressure in group A (137.1 + 34.5, 134.5+23.2mmHg) was significantly higher tha...
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