目的 研究阿魏酸钠(soaium ferulate,SF)对L-精氨酸诱导的大鼠重症急性胰腺炎(severeacute pancreatitis,SAP)的治疗作用及其机制.方法 将60只成年SD大鼠随机分为对照组、SAP组、SF组,每组20只.采用腹腔内分两次注射大剂量L-精氨酸(2.5g/kg×2,间隔1 h)的方法制备SAP大鼠模型,SAP组和SF组大鼠分2次间隔1 h腹腔内注射20%L-精氨酸溶液(2.5 g/kg×2);对照组同法予等量生理盐水.5 min后,SF组大鼠再尾静脉注射SF注射液100 mg/kg,q d×3 d,其余两组同法予等量生理盐水.72 h后比较三组大鼠腹水性状、胰腺组织病理变化和血清淀粉酶(AMY)、内皮素-1(ET-1),TNF-α,IL-6水平和胰腺组织丙二醛(MDA)、超氧化物歧化酶(SOD)、还原型谷胱甘肽(GSH)含量及预后.计量资料组间比较用单因素方差分析,计数资料用Fisher确切概率法检验,以P<0.05为差异有统计学意义.结果 72 h后与对照组比较,SAP组出现典型的SAP病理形态改变,且大鼠血清AMY,ET-1,TNF-α,IL-6及胰腺组织NDA均显著升高[(9715.5±301.3)IU/L vs.(729.2±134.2)IU/L;(25.32±3.67)ng/L vs.(14.32±2.69)ng/L;(102.95±11.24)ng/L.vs.(38.62±3.87)ng/L;(538.63±9.53)ng/L vs.(186.35±1.19)ng/L;(34.8±3.9)mol/kg vs.(8.1±2.1)mol/kg,均P<0.01],胰腺组织抗氧化物质GSH,SOD明显降低[(7.1±0.6)mg/kg、vs.(16.9±1.9)mg/kg;(6423±1978)kU/kg vs.(29 905±z945)kU/kg,均P<0.01];与SAP组比较,SF组胰腺组织病理损害减轻且组织病理评分较低(P<0.05),血清AMY,ET-1,TNF-α,IL-6及胰腺组织NDA明显降低[(8104.6±149.9)IU/L vs.(9715.5±301.3)IU/L;(20.26±5.86)ng/L vs.(25.32±3.67)ng/L;(84.19±15.14)hg/L vs.(102.95±11.24)ng/L;(458±5.37)mol/kg vs.(538.63±9.53)ng/L;(28.3±2.5)mot/kg vs.(34.8±3.9)mol/kg,均P<0.05],胰腺组织GSH、SOD升高[(8.5±1.4)mg/kg vs.(7.1±0.6)mg/kg;(10316±2810)kU/kg、rs.(6423±1978)ldJ/kg,均P<0.05];SF组72 h死亡率低于SAP组,但差异无统计学意义(P=0.25).结论 SF能清除氧自由基、提高胰腺组织抗氧化物质SOD和GSH含量,降低血清促炎细胞因子及ET-1水平,减轻胰腺组织的病理损害,并且有可能降低死亡率,在SAP治疗中具有独特的优势.
目的 研究阿魏痠鈉(soaium ferulate,SF)對L-精氨痠誘導的大鼠重癥急性胰腺炎(severeacute pancreatitis,SAP)的治療作用及其機製.方法 將60隻成年SD大鼠隨機分為對照組、SAP組、SF組,每組20隻.採用腹腔內分兩次註射大劑量L-精氨痠(2.5g/kg×2,間隔1 h)的方法製備SAP大鼠模型,SAP組和SF組大鼠分2次間隔1 h腹腔內註射20%L-精氨痠溶液(2.5 g/kg×2);對照組同法予等量生理鹽水.5 min後,SF組大鼠再尾靜脈註射SF註射液100 mg/kg,q d×3 d,其餘兩組同法予等量生理鹽水.72 h後比較三組大鼠腹水性狀、胰腺組織病理變化和血清澱粉酶(AMY)、內皮素-1(ET-1),TNF-α,IL-6水平和胰腺組織丙二醛(MDA)、超氧化物歧化酶(SOD)、還原型穀胱甘肽(GSH)含量及預後.計量資料組間比較用單因素方差分析,計數資料用Fisher確切概率法檢驗,以P<0.05為差異有統計學意義.結果 72 h後與對照組比較,SAP組齣現典型的SAP病理形態改變,且大鼠血清AMY,ET-1,TNF-α,IL-6及胰腺組織NDA均顯著升高[(9715.5±301.3)IU/L vs.(729.2±134.2)IU/L;(25.32±3.67)ng/L vs.(14.32±2.69)ng/L;(102.95±11.24)ng/L.vs.(38.62±3.87)ng/L;(538.63±9.53)ng/L vs.(186.35±1.19)ng/L;(34.8±3.9)mol/kg vs.(8.1±2.1)mol/kg,均P<0.01],胰腺組織抗氧化物質GSH,SOD明顯降低[(7.1±0.6)mg/kg、vs.(16.9±1.9)mg/kg;(6423±1978)kU/kg vs.(29 905±z945)kU/kg,均P<0.01];與SAP組比較,SF組胰腺組織病理損害減輕且組織病理評分較低(P<0.05),血清AMY,ET-1,TNF-α,IL-6及胰腺組織NDA明顯降低[(8104.6±149.9)IU/L vs.(9715.5±301.3)IU/L;(20.26±5.86)ng/L vs.(25.32±3.67)ng/L;(84.19±15.14)hg/L vs.(102.95±11.24)ng/L;(458±5.37)mol/kg vs.(538.63±9.53)ng/L;(28.3±2.5)mot/kg vs.(34.8±3.9)mol/kg,均P<0.05],胰腺組織GSH、SOD升高[(8.5±1.4)mg/kg vs.(7.1±0.6)mg/kg;(10316±2810)kU/kg、rs.(6423±1978)ldJ/kg,均P<0.05];SF組72 h死亡率低于SAP組,但差異無統計學意義(P=0.25).結論 SF能清除氧自由基、提高胰腺組織抗氧化物質SOD和GSH含量,降低血清促炎細胞因子及ET-1水平,減輕胰腺組織的病理損害,併且有可能降低死亡率,在SAP治療中具有獨特的優勢.
목적 연구아위산납(soaium ferulate,SF)대L-정안산유도적대서중증급성이선염(severeacute pancreatitis,SAP)적치료작용급기궤제.방법 장60지성년SD대서수궤분위대조조、SAP조、SF조,매조20지.채용복강내분량차주사대제량L-정안산(2.5g/kg×2,간격1 h)적방법제비SAP대서모형,SAP조화SF조대서분2차간격1 h복강내주사20%L-정안산용액(2.5 g/kg×2);대조조동법여등량생리염수.5 min후,SF조대서재미정맥주사SF주사액100 mg/kg,q d×3 d,기여량조동법여등량생리염수.72 h후비교삼조대서복수성상、이선조직병리변화화혈청정분매(AMY)、내피소-1(ET-1),TNF-α,IL-6수평화이선조직병이철(MDA)、초양화물기화매(SOD)、환원형곡광감태(GSH)함량급예후.계량자료조간비교용단인소방차분석,계수자료용Fisher학절개솔법검험,이P<0.05위차이유통계학의의.결과 72 h후여대조조비교,SAP조출현전형적SAP병리형태개변,차대서혈청AMY,ET-1,TNF-α,IL-6급이선조직NDA균현저승고[(9715.5±301.3)IU/L vs.(729.2±134.2)IU/L;(25.32±3.67)ng/L vs.(14.32±2.69)ng/L;(102.95±11.24)ng/L.vs.(38.62±3.87)ng/L;(538.63±9.53)ng/L vs.(186.35±1.19)ng/L;(34.8±3.9)mol/kg vs.(8.1±2.1)mol/kg,균P<0.01],이선조직항양화물질GSH,SOD명현강저[(7.1±0.6)mg/kg、vs.(16.9±1.9)mg/kg;(6423±1978)kU/kg vs.(29 905±z945)kU/kg,균P<0.01];여SAP조비교,SF조이선조직병리손해감경차조직병리평분교저(P<0.05),혈청AMY,ET-1,TNF-α,IL-6급이선조직NDA명현강저[(8104.6±149.9)IU/L vs.(9715.5±301.3)IU/L;(20.26±5.86)ng/L vs.(25.32±3.67)ng/L;(84.19±15.14)hg/L vs.(102.95±11.24)ng/L;(458±5.37)mol/kg vs.(538.63±9.53)ng/L;(28.3±2.5)mot/kg vs.(34.8±3.9)mol/kg,균P<0.05],이선조직GSH、SOD승고[(8.5±1.4)mg/kg vs.(7.1±0.6)mg/kg;(10316±2810)kU/kg、rs.(6423±1978)ldJ/kg,균P<0.05];SF조72 h사망솔저우SAP조,단차이무통계학의의(P=0.25).결론 SF능청제양자유기、제고이선조직항양화물질SOD화GSH함량,강저혈청촉염세포인자급ET-1수평,감경이선조직적병리손해,병차유가능강저사망솔,재SAP치료중구유독특적우세.
Objective To study the therapeutic effects and mechanism of Sodium Fendate(SF) on rats with severe acute pancreatitis(SAP) induced by L-arginine. Method A total of 60 adult SD rats were randomly and e-qually divided into control group, SAP group and SF group, with 20 rats in each group. The rat model of SAP wes established by injecting 2.5 g/kg L-arginine at a dose of intraperitoneally twice at an interval of 1 hour, and rats in SAP group and SF groups were administrated intraperitoneally with 20% L-arginine solution(2.5 g/kg×2) twice at an interval of 1 hour; rats in control group were injected intraperitoneally with the same volume of physiological saline twice alone.At 5 minutes after L-arginine administration,rats in SF group were injected with SF solution (100 mg/kg, qd×3 d) via the tail vein, and rats in the other two groups received a sham injection of the same volume of physiological saline alone. The characteristics of ascites, the pathological changes of pancreatic tissue and the serum levels of amylase(AMY), endothelin-l(ET-1), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and the contents of malonaldehyde (MDA), suede dismutase (SOD), reduced glutathioue (GSH) of pan-creatic tissue of rats and prognosis were compared at 72 hours after L-arginine administration. Measurement data were evaluated by oue-way ANOVA, and numeration data were assessed by Fisher' s exact test. P<0.05 was considered statistically significant. Results Compared with control group,at 72 hours after L-arginine administra-tion,rats in SAP group presented characteristically histopathological changes of SAP with significantly higher serum levels of AMY, ET-1, TNF-α, IL-6 and MDA of pancreatic tissue[(9715.5±301.3) IU/L vs. (729.2±134.2) IU/L;(25.32±3.67) ng/L vs. (14.32±2.69) ng/L;(102.95±11.24) ng/L vs. (38.62±3.87) ng/L; (538.63±9.53) ng/L vs. (186.35±1.19) ng/L;(34.8±3.9) mol/kg vs. (8.1±2.1) mol/kg, all P< 0.01], and lower GSH and SOD in the pancreatic tissue[(7.1±0.6) mg/kg vs. (16.9±1.9) mg/kg; (6423± 1978) kU/kg vs. (29905+2945) kU/kg,both P<0.01].Compared with SAPmodel group,at 72 hours after ad-ministration of L-arginiue, the pathological lesions of SAP in rats of SF group were significantly alleviated with lower pathological scores (P<0.05), lower serum levels of AMY, ET-1 ,TNF-α,IL-6 and MDA in the pancreatic tissue [(8104.6±149.9) IU/L vs. (9715.5±301.3) IU/L; (20.26±5.86) ng/L vs. (25.32±3.67) ng/L; (84.19±15.14) ng/L vs. (102.95±11.24) ng/L;(458±5.37) mol/kg vs. (538.63±9.53) rig/L;(28.3±2.5) moL/kg vs. (34.8±3.9) mol/kg,all P<0.05], and higher SOD and GSH in the pancreatic tissue[(8.5 ±1.4) mg/kg vs. (7.1±0.6) mg/kg;(10 316±2810) kU/kg vs. (6423±1978) kU/kg, both P<0.05].At 72 hours the death rate in SF group was lower than that in SAP group,but the difference had no significance (P= 0.2.5). Conclusions SF can scavenge oxygen-derived free radicals, upgrade the contents of SOD and GSH of pancreatic tissue,decrease the levels of serum proinflammatory cytokines and ET-1, ameliorate the pathological le-sions of pancreatic tissue in rats,and has the capability of decreasing death rate, so it possesses a distinct advantage for the treatment of SAP.
