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丹参多酚酸对重症急性胰腺炎肾损伤影响的实验研究
The study of effect of salvianolate on renal injury in rats with severe acute pancreatitis
【作者】 范立侨; 李勇; 晋潇; 王力利; 赵群; 赵雪峰; 王冬; 刘庆伟;
【Author】 FAN Li-qiao;LI Yong;JIN Xiao;WANG Li-li;ZHAO Qun;ZHAO Xue-feng;WANG Dong;Department of General Surgery,the Fourth Affiliated Hospital,Hebei Medical University;
【机构】 河北医科大学第四医院外三科;
【摘要】 目的制备大鼠SAP模型,并与行颈部胸导管穿刺引流淋巴液之后对比检测大鼠血清淀粉酶(AMY)、肌酐(CR)、尿素氮(BUN)等指标的变化,胸导管引流淋巴液中内毒素含量的变化。旨在揭示SAP并发肾损伤的机制,并发现有效的干预措施,为今后指导临床治疗提供实验依据。方法 SD雄性大鼠随机分成:颈部假手术组+腹部假手术组(J组);颈部假手术组+SAP组(SAP组);SAP+丹参多酚酸给药组(D组);实验采用以5%牛磺酸胆酸钠溶液经胰胆管逆行缓慢注射诱导制备SAP模型,干预组按要求经尾静脉给予缓慢注射丹参多酚酸。于术后2、6、12h进行胰腺、肾脏组织大体观察,测量腹水量,留取血清、血浆样本及组织标本。肉眼观察组织大体形态变化,光镜下测定胰腺及肾脏的病理评分。检测血清淀粉酶(AMY)、肌酐(CR)、尿素氮(BUN),血清过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-PX)的含量。结果:2、SAP组大鼠有明显大量的腹水,颜色暗红,且随着时间的延长,腹水量增大,颜色加深;胰腺大体所见有广泛明显充血水肿,片状出血和黑色坏死,6h组及12h组存在散在皂化斑,胰腺病理评分明显增高(P<0.01)。肾脏SAP 12h组表面暗红、有肿胀。血清肌酐(CR)、尿素氮(BUN)含量明显升高(P<0.01),且随时间延长进一步升高;血清过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-PX)水平明显降低(P<0.01)。5、D组与SAP组比较,腹水量明显减少(P<0.01),胰腺病理评分明显降低(P<0.01),肾脏病理损伤减轻,血清AMY、肌酐(CR)、尿素氮(BUN)浓度明显降低(P<0.05,或P<0.01),且随时间延长而明显降低;血清过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-PX)水平明显降低(P<0.01)。结论:1.SAP时引起了肾损伤性变化,肾功能受到影响。3.在SAP伴AKI时,血清、淋巴液、胰腺及肾组织匀浆中CAT、GSH-PX缺乏,说明机体抗氧化能力下降。5应用丹参多酚酸能通过改善全身微循环、清除氧自由基等作用减轻SAP时肾的损害程度。
【Abstract】 Objective:In this study,the SAP model in rats was made by retrograde inject into biliopancreatic duct with 5%sodium taurocholate.Then according to detect the change of the level of creatinine(CR),blood urea nitrogen(BUN) in blood and endotoxin in thoracic duct lymph drainage,to find difference between SAP rats,neck duct lymph drainage and after Salvianolate’s intravenous injection.The purpose of this study is to reveal the mechanism of kidney injury in SAP in rats,by the way,also to find effective treatment and provide an experiment’s support for clinical practice.Methods:Healthy male SD rats,weight of 330 ± 30g,were divided randomly.Including:cervical sham operation group + abdominal sham operation group(J group);cervical sham operation group + SAP group;SAP + salvianolate group(D group).In this experiment the SAP model in rats was made by retrograde inject into biliopancreatic duct with 5%sodium taurocholate.And then set up channels via tail vein to infuse liquid,each group of rows as required slowly injected salvianolate via the tail.At a predetermined time points after2,6,12h,we can observe renal tissue,measure the amount of ascites.collect serum specimens,plasma and tissue samples.Thoracic duct lymph drainage group need collect lymph per hour.Observing organize’s changes,deterrnining the pathology score of pancreas and kidney under the light microscopy,determining the content of the serum amylase(AMY),creatinine(CR),blood urea nitrogen(BUN),serum catalase(CAT) and glutathione peroxidase(GSH-PX) and thoracic duct lymph drainage.Result:2.Compared with J and Sham group,the color of ascites is getting dark,and the amount of ascites is increasing with time in rats of SAP group,A wide range of significant edema,piece bleeding and black necrosis in pancreas,can be generally seen in6h and 12h group.Saponification spots were found on the surface of pancreas.The kidney of SAP12h group become swelling and has a dark red surface.The levels of serum AMY,creatinine(CR),blood urea nitrogen(BUN) were significantly higher(P <0.01),and increased with time;The activity of plasma catalase(CAT) and glutathione peroxidase(GSH-PX) were significantly lower(P <0.01).5.Compared with SAP group,the amount of ascites in D group is lower(P <0.01),pancreatic pathology score was significantly lower(P <0.01),The content of serum AMY,creatinine(CR),blood urea nitrogen(BUN) were significantly lower(P <0.05,or P <0.01),and obvious decreased with time(P <0.05,or P <0.01);The activity of plasma catalase(CAT) and glutathione peroxidase(GSH-PX) were significantly lower(P<0.01).Conclusion:1.Renal parenchymal of SAP model rats shows extensive bleeding,renal tubular epithelial cell necrosis,renal interstitial congestion,inflammatory cell infiltration,tubular stenosis,blockage and other pathological changes,The contents of AMY,CR,BUN significantly increased in serum.The activity of CAT and GSH-PX in renal tissue were significantly reduced.Indicating that kidney injury occurred in SAP and renal function is impaired.3.In SAP with AKI,the activity of CAT,GSH-PX in serum,lymph,pancreas and kidney tissue homogenates decreased.It indicated that the body’santioxidant capacity declined.5.The intraveuous injection salvianolate improved systemic microcirculation,scavenged oxygen free radicals,and reduced the degree of renal damage in SAP
【Key words】 severe acute pancreatitis; kidney injury; endotoxin; catalase; glutathione peroxidase; salvianolate;
- 【会议录名称】 第9届全国胃癌学术会议暨第二届阳光长城肿瘤学术会议论文汇编
- 【会议名称】第9届全国胃癌学术会议暨第二届阳光长城肿瘤学术会议
- 【会议时间】2014-06-27
- 【会议地点】中国北京
- 【分类号】R657.51
- 【主办单位】中国抗癌协会胃癌专业委员会