摘要
[目的]探讨双镜经胆囊管汇入部微切开并置入支架治疗胆道结石的治疗效果,并通过观察黏蛋白5 AC(MUC5 AC)、胆囊收缩素受体A(CCKAR)变化,对胆道结石形成的机制,尤其对治疗和预后监测的重要分子标记物,提供探索性指导和借鉴.[方法]选取胆管结石合并胆囊结石患者300例为研究对象,根据治疗方法分为对照Ⅰ组、对照Ⅱ组和实验组,每组100例.对照Ⅰ组采取腹腔镜胆总管切开胆道镜取石、T管引流术;对照Ⅱ组采取腹腔镜下胆囊切除术、胆总管切开胆道镜取石,内镜下于胆总管内留置鼻胆管;实验组采用双镜经胆囊管汇入部微切开并于胆总管内置入胰管支架.收集围手术期情况,对手术前后的血清丙氨酸氨基转移酶(ALT)等肝胆指标,MUC5 AC、CCKAR、总胆汁酸(TBA)、胆囊收缩素18(CCK-18),白细胞介素-6(IL-6),肿瘤坏死因子-α(TNF-α)含量以及并发症情况进行对比,随访术后1年复发情况.[结果]实验组术中出血量、引流量、手术时间、住院时间显著低于对照Ⅰ组和对照Ⅱ组(P<0.05);取石时间较其他2组无明显差异,术后3组患者丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TBil)、白细胞(WBC)、皮质醇(Cor)较术前显著降低,且实验组低于对照Ⅰ组和对照Ⅱ组(P<0.05);术后实验组炎症因子IL-6,TNF-α低于对照Ⅰ组和对照Ⅱ组(P<0.05);实验组并发症发病率显著低于对照Ⅰ组和对照Ⅱ组(P<0.05),3组结石残留率比较无显著差异(P>0.05);3组治疗有效率比较无显著差异,术后5年实验组复发率显著低于对照Ⅰ组和对照Ⅱ组(P<0.05).3组血清MUC5 AC治疗后显著降低(P<0.05),血清CCKAR治疗后显著升高(P<0.05),实验组变化较明显;MUC5 AC、CCKAR治疗前差异无统计学意义(P<0.05).UC5 AC、CCKAR在胆道结石患者胆囊组织中表达与正常胆囊组织比较差异有统计学意义(P<0.05).MUC5 AC在胆道结石胆囊组织染色面积较大且颜色较深,呈较高表达;CCKAR在正常对照组织中染色面积较大且颜色较深,呈较高表达.胆道结石患者胆囊组织MUC5 AC蛋白表达量明显高于正常对照组织(P<0.05),CCKAR蛋白表达量明显低于正常对照组织(P<0.05).血清MUC5 AC与ALT、AST、TBil、WBC、IL-6、TNF-α有显著正相关性(P<0.05),与Cor有显著负相关性(P<0.05).血清CCKAR与ALT、AST、TBil、WBC、IL-6、TNF-α有显著负相关性(P<0.05),与Cor有显著正相关性(P<0.05).[结论]采用双镜经胆囊汇入部微切并置入支架治疗胆道结石能缩短住院时间、降低并发症和复发率,并可降低MUC5 AC水平、提高CCKAR水平,MUC5 AC、CCKAR可能在胆道结石的预后治疗中具有潜在重要意义.
Abstract
[Objective]To explore the therapeutic effect of choledocholithiasis treated by microincision and stent placement through the entrance of cystic duct.by observing the changes of MUC5 AC and CCK-AR,and provide exploratory guidance and reference for the mechanism of bile duct stone formation,espe-cially searching the important molecular markers of treatment and prognosis monitoring.[Methods]The to-tals of 300 patients with cholangiolithiasis combined with cholecystolithiasis were selected as the study ob-jects,and were divided into control group Ⅰ,control group Ⅱ and experimental group according to treat-ment methods,with 100 cases in every group.The control group Ⅰ underwent laparoscopic choledochoto-my,choledochoscopy and T-tube drainage;the control group Ⅱ underwent laparoscopic cholecystectomy,choledochotomy and choledochoscopy,and retained nasobiliary duct in the common bile duct;the experi-mental group underwent double endoscopy,microincision through the cystic duct and built-in pancreatic duct stent in the common bile duct.We collected the perioperative situation,compared the serum alanine aminotransferase(ALT)and other hepatobiliary indexes,MUC5 AC,CCKAR,TBA,CCK-18,IL-6,TNF-a content and complications before and after the operation,and followed up the recurrence situation one year after the operation.[Results]The bleeding volume,drainage volume,operation time,stone taking time and hospitalization time in the experimental group were significantly lower than those in the control group Ⅰand the control group Ⅱ(P<0.05).The alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),leukocyte(WBC),cortisol(COR)in the experimental group were significant-ly lower than those in the two control groups(P<0.05.The levels of IL-6 and TNF-α in experimental group were lower than those in control group(P<0.05);the incidence rate of complications in the experi-mental group was significantly lower than that in the two control group(P<0.05),and there was no signif-icant difference in the residual stone rate between the three groups(P>0.05).The effective rate of the three groups was not significantly different,and the recurrence rate of the experimental group was signifi-cantly lower than that of the two control group 5 years after operation(P<0.05).Serum MUC5 AC in the three groups was significantly decreased after treatment(P<0.05),and serum CCKAR was significantly increased after treatment(P<0.05).There was no significant difference between MUC5 AC and CCKAR before treatment(P<0.05).The expression of MUC5 AC and CCKAR in gallbladder tissues of patients with biliary calculi was significantly different from that of normal gallbladder tissues(P<0.05).MUC5 AC was highly expressed in gallbladder tissues of patients with biliary calculi with large staining area and dar-ker color.CCKAR was highly expressed in normal tissues with large staining area and dark color.The ex-pression of MUC5 AC protein in biliary calculi group was significantly higher than that in healthy control group(P<0.05),and the expression of CCKAR protein was significantly lower than that in healthy control group(P<0.05).Serum MUC5 AC was significantly positively correlated with ALT,AST,TBil,WBC,IL-6 and TNF-α(P<0.05),and significantly negatively correlated with Cor(P<0.05).Serum CCKAR was significantly negatively correlated with ALT,AST,TBil,WBC,IL-6 and TNF-α(P<0.05),and significant-ly positively correlated with Cor(P<0.05).[Conclusion]To sum up,the treatment of biliary calculi with double mirror micro incision through the confluence of gallbladder and stent placement can shorten the hos-pital stay,reduce the complications and recurrence rate,reduce the level of MUC5 AC and improve the level of CCKAR.MUC5 AC and CCKAR may have potential significance in the prognosis and treatment of bili-ary calculi.
基金项目
2020年度河北省医学科学研究课题计划(20200401)