一氧化氮在伴高脂血症急性出血坏死性胰腺炎大鼠胰腺及肾损害中的作用

Nitric oxide protects against pancreatic and renal injury in rats with acute necrotizing pancreatitis and hyperlipidemia

目的:探讨一氧化氮(NO)含量变化对伴高脂血症急性出血坏死性胰腺炎(ANP)大鼠胰腺、肾损害的作用和对肾小球足细胞的影响.方法:♂SD大鼠30只,高脂饲料喂养4wk建立大鼠高脂血症模型,将大鼠随机等分为3组;A组即高脂血症+A N P;B组即高脂血症+ANP+L-精氨酸(L-arg);C组即高脂血症+ANP+L-硝基精氨酸甲基酯(L-name),3组均逆行胰胆管注射3.5%牛磺脱氧胆酸钠制作大鼠SAP模型.A组给予适量生理盐水,B组给予L-arg,每次250mg/kg,C组给予L-name,每次10mg/kg,3组均在造模前30min和造模后2h给药.术后6h监测血清淀粉酶(Amyl)、肌酐(Cr)、血尿素氮(BUN)、NO水平,胰腺组织NO和内皮型一氧化氮合成酶(eNOS)含量变化,光镜观察胰腺组织病理学变化,电镜观察肾小球足细胞病理学变化,免疫组织化学技术分析肾小球足细胞nephrin蛋白的表达情况.结果:与B组比较,A、C组Amyl(U/L)、C r(μm o l/L)、BU N(m m o l/L)水平显著升高(Amyl:4219.8±900.0,6643.2±1135.4vs2434.4±831.6;Cr:15.8±1.6,22.4±3.3vs9.9±0.8;BUN:135.9±23.6,206.4±23.4vs103.2±13.2,均P<0.01),胰腺组织及肾脏足细胞损伤加重,血清和胰腺组织NO(μmol/L)水平显著降低(59.46±11.21,44.84±10.72vs78.88±9.76;5.23±0.48,4.39±0.45vs6.18±0.57,均P<0.01),胰腺组织eNOS、肾脏足细胞nephrin蛋白表达降低.结论:在伴高脂血症ANP合并肾功能障碍时,eNOS催化产生的NO不仅可以保护胰腺组织,并且对肾小球足细胞和肾脏功能也具有一定的保护作用.

AIM：To determine whether nitric oxide（NO） protects against pancreatic and renal injury in rats with acute necrotizing pancreatitis（ANP） and hyperlipidemia.METHODS：Forty male Sprague-Dawley rats were fed a high-fat diet for 4 weeks to induce hyperlipidemia.The rats were randomly divided into three groups：group A（hyperlipidemia＋ ANP＋normal saline）,group B（hyperlipidemia ＋ANP＋L-arg）,and group C（hyperlipidemia ＋ANP＋L-Name）.ANP was induced by retrograde injection of 3.5%sodium taurocholate into the biliopancreatic duct.Each group was treated 30 min before and 2 h after ANP induction.At 6 h after ANP induction,serum amylase（Amyl）,creatinine（Cr）,urea nitrogen（BUN）,NO,and pancreatic NO and endothelial nitric oxide syn-thetase（eNOS）were measured;pancreatic histopathology was detected by light microscopy;ultrastructure of glomerular podocytes was observed by election microscopy;and expression of nephrin in glomerular podocytes was examined by immunohistochemistry.RESULTS：Serum Amyl,Cr and BUN in group B were significantly lower than those in groups A and C（Amyl：4 219.8±900.0,6 643.2±1 135.4 vs 2 434.4±831.6;Cr：15.8±1.6,22.4±3.3 vs 9.9 ±0.8;BUN：135.9±23.6,206.4±23.4 vs 103.2± 13.2;all P0.01）.Pancreatic injury and changes in glomerular podocytes were milder in group B than in groups A and C.The levels of serum and pancreatic NO（59.46±11.21,44.84±10.72 vs 78.88±9.76;5.23±0.48,4.39±0.45 vs 6.18±0.57;all P0.01）and pancreatic eNOS,and expression of nephrin in glomerular podocytes were significantly higher in group B than in groups A and C.CONCLUSION：NO produced by eNOS can protect against pancreatic and renal injury in rats with ANP and hyperlipidemia.