| Objective First, to investigate the short and long term's therapeutic effects of prostaglandin E1(PGEl) in diabetes patients with nephropathy(DN). Then, to explore the possible therapeutic mechanism of Prostaglandin El in reversing diabetic nephropathy by:(1)testing the level of Endothelin-1(ET-1)and AngiotentionⅡ(AngⅡ) in plasma and Renal cortex (2) observing apoptosis in the renal tissue.Methods 1. Clinical part of research:Patients with DN stageⅢto stageⅤaccording to Mogensen diabetic nephropathy diagnostic criteria were randomly received PGEl (prostaglandin E1, PGEl group), PGEl+ACEI(angiotensin-converting enzyme inhibitor, PGEl+ACEI group), ACEI mono-therapy (ACEI group) and blank (control group) therapy. Proteinuria and albuminuria were measured before and after treatment for 15 days,6months and 18months. Patients with stageⅣnephropathy were further subdivided into three groups according to their amounts of proteinuria: early stageIV(the protienuria was less than 1.5g/d), middle stageIV(the protienuria was between 1.5g/d and 2.5g/d) and late stageIV(the protienuria was larger than 2.5g/d).2. Animal experiment:55 male Wistar rats were intraperitoneally injected w ith streptozotocin(STZ)a to develop an animal model of DN.46 successfully m odeled rats rats were randomly divided into four groups:PGE1 group, ACEI gr oup, PGE1+ ACEI group, DN group, and 10 normal rats as control. The rats of PGE1 group were given PGE1 intravenouly at the dose of 10μg/kg·d×10 d; The rats of ACEI group were given ACEI orally at the dose of 10 mg/kg-dx 8W; The rats of PGE1+ ACEI group were given both PGE1 and ACEI as the same dose as the upper two groups. The rats of DN group and control group were given saline only. Experimental evaluation:①BUN(blood urea nitrogen), Scr(serium creatine),Albuminuria②Renal hypertrophy index③Renal pathological morphology by HE staining④ET-l,Ang II level in plasma and renal cortex by r adioimmunoassay⑤Apoptosis of renal cells in situ by TUNEL testResults 1. Clinical Research:(1) After treatment, the proteinuria and albuminuria of patients with stageⅢand early stageⅣdescended significantly in all treated groups(P<0.01) during follow-up period. (2) There was significant difference in patients with stage V nephropathy at the end of six months follow-up after treatment (P<0.05), but that did not show in PGE1 group compared with that pre-treatment(P>0.05). (3) The level of these incidicators still decreased in PGE1+ACEI group(P<0.01orP<0.05) but elevated in PGE1 group(P<0.05) compared with that pre-treatment in patients with middle stageⅣand late stageⅣnephropathy at the end of 18 months. The level of these incidicators of patients with stageⅤelevated compared with that pre-treatment in all treated groups(P<0.01).2.animal experiment:①Albuminuria:10 day after treatment, the albuminuria decreased in therapeutic group, especially in PGE1+ ACEI group. The albumin level grads were as following:DN group>ACEI group>PGE1 group>PGE1+ ACEI group>control group(P<0.01); 8 week after treatment, the albumin level grads were was as following:DN group> PGE1 group> ACEI group>PGE1+ ACEI group> control group(P<0.01 or P<0.05).②BUN,Scr and Renal hypertrophy index:After treatment,these three indexes had the same statistical significance.The level of them decreased in therapeutic group, most obviously in PGE1+ ACEI group, their grads were as following:DN group>all treated group>control group(P<0.01 or P<0.05)③Renal pathological morphology:in DN group, swelling, basement membrane thickening and mesangial broadening were observed in the majority of renal glomerular. Part of the renal tubular became degeneration and lumen was narrowed; Pathological manifestations of all treatment groups became better than DN group and that of the PGE1+ ACEI group was the best.④ET-1,AngⅡlevels in plasma and renal cortex:The levels of them from high to low was:DN group> PGE1 group>ACEI group>PGE1+ ACEI group> control group(P<0.01 or P<0.05).what's more,the intergroup differences were more significant in renal cortex(P<0.01)than in plasma(P<0.05)⑤TUNEL test:The apoptotic cells were mainly located in the region of renal tubular.The number of apoptotic cells in renal tubular from high to low were: DNgrouP>all treated grouP> control group(P<0.05), the apoptotic cells were the lowest in PGE1+ ACEI group(P<0.05).Conclusion 1. The short term therapeutic effects of PGE1 are quick and good in patients with diabetic nephropathy. The earlier, the treatment, the better, the therapeutic effect, especially in patients with stageⅢnephropathy compared with stageⅤ.2. The combination of PGE1 and ACEI will get the best therapeutic effects and is more effective than PGE1 or ACEI alone, especially in stageⅢnephropathy and for long term.3.PGE1 may reverse DN by decreasing not only the level of ET-1, AngⅡin renal cortex but also the number of apoptotic cells in renal tubular.
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