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| 1 | Caspase-1 inhibition alleviates acute renal injury in rats with severe acute pancreatitis显示文摘AIM:To assess the effect of inhibition of caspase-1 on acute renal injury in rats with severe acute pancreatitis(SAP).METHODS:Forty-two Sprague-Dawley rats were randomly divided into three groups:healthy controls(HC,n=6),SAP rats treated with saline(SAP-S,n=18),or SAP rats treated with a caspase-1/interleukin(IL)-1β-converting-enzyme(ICE)inhibitor(SAP-I-ICE,n=18).SAP was induced by retrograde infusion of 5%sodium taurocholate into the bile-pancreatic duct.HC rats were subjected to identical treatment and surgical procedures without sodium taurocholate.Rats received an intraperitoneal injection of isotonic saline(SAP-S)or the inhibitor(SAP-ICE-I)at 2 and 12 h after induction of acute pancreatitis.Surviving rats were sacrificed at different time points after SAP induction;all samples were obtained and stored for subsequent analyses.The levels of blood urea nitrogen(BUN)and creatinine(Cr)were measured using automatic methods,and serum IL-1βconcentrations were measured by an enzymelinked immunosorbent assay.Intrarenal expression of IL-1β,IL-18 and caspase-1 mRNAs was detected by RT-PCR.IL-1βprotein expression and the pathologic changes in kidney tissues were observed by microscopy after immunohistochemical or hematoxylin and eosin staining,respectively.RESULTS:The serum levels of BUN and Cr in the SAP-S group were 12.48±2.30 mmol/L and 82.83±13.89μmol/L at 6 h,23.53±2.58 mmol/L and 123.67±17.67μmol/L at 12 h,and 23.60±3.33 mmol/L and125.33±21.09μmol/L at 18 h,respectively.All were significantly increased compared to HC rats(P<0.01for all).Levels in SAP-ICE-I rats were significantly decreased compared to SAP-S rats both at 12 and 18 h(P<0.01 for all).Serum IL-1βlevels in the SAP-S group were 276.77±44.92 pg/mL at 6 h,308.99±34.95pg/mL at 12 h,and 311.60±46.51 pg/mL at 18 h;all significantly higher than those in the HC and SAP-ICE-I groups(P<0.01 for all).Intrarenal expression of IL-1βmRNA was weak in HC rats,but increased significantly in SAP-S rats(P<0.01).ICE inhibition significantly decreased the expression of IL-1βand IL-18 mRNAs(P<0.05 for all vs SAP-S),whereas caspase-1 mRNA expression was not significantly different.Weak IL-1βimmunostaining was observed in HC animals,and marked staining was found in the SAP-S group mainly in renal tubular epithelial cells.IL-1βimmunostaining was significantly descended in SAP-ICE-I rats compared to SAP-S rats(P<0.05).Caspase-1 inhibition had no effect on the severity of kidney tissue destruction.CONCLUSION:The expression of caspase-1-activated cytokines IL-1βand IL-18 plays a pivotal role in acute renal injury in rats with experimental SAP.Caspase-1inhibition improves renal function effectively. | Xiao-Hua Zhang Min-Li Li Bin Wang Mei-Xia Guo Ren-Min Zhu | 2014 | World Journal of Gastroenterology2014,20,30: | 13 |
| 2 | 痰热清注射液对重症急性胰腺炎大鼠肺损伤保护作用的初步研究显示文摘目的观察痰热清注射液对重症急性胰腺炎大鼠肺损伤的保护作用。方法选择96只健康SD大鼠随机分为对照组、假手术组、模型组及痰热清组,采用5%牛磺胆酸钠逆行胰胆管注射法建立SAP大鼠模型,以建模后6、12 h及24 h,分为3个亚组(每组8只)。观察肺损伤指数,分别采用酶联免疫法、半定量逆转录PCR法及蛋白印迹技术检测不同时间点肺组织中RNA及高迁移率族蛋白水平。结果模型组较对照组和假手术在肺损伤指数、细胞间粘附分子-1(ICAM-1)、白介素-18(IL-18)、骨髓系细胞触发受体(TREM-1)m RNA及高迁移率族蛋白-1(HMGB1)方面差异均有统计学意义(P<0.01),而痰热清组治疗后较模型组ICAM-1、IL-18、TREM-1 m RNA和HMGB1等水平有降低(P<0.01),肺损伤指数明显降低(P<0.01)。结论痰热清注射液能降低重症急性胰腺炎大鼠肺组织中ICAM-1、IL-18、TREM-1 m RNA及高迁移率族蛋白B1水平的表达,有效缓解重症急性胰腺炎大鼠的肺损伤。 | 赵中江 邓哲 孙冀武 刘德红 | 2015 | 中国中医急症2015,24,4: | 8 |
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