利胆健脾法为主预防胆囊结石的作用及机制研究
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摘要
目的:探讨中医利胆健脾法为主预防微创保胆取石术(MC)后胆囊结石复发以及对豚鼠胆囊收缩素受体(CCK-AR)的机制。方法:临床研究中,将微创保胆取石术(MC)后患者73例,随机分为对照组34例,中药组34例。中药组术后第4天服用利胆健脾法为主方药,对照组未进行任何治疗。术后1年统计疗效(胆囊壁厚度、胆囊收缩率),进行比较;实验研究中,将90只豚鼠随机分为空白组,模型组和治疗组,每组30只,分别喂食标准饲料、致石饲料、致石饲料加防石胶囊,2个月后处死取材,用RT-PCR法检测胆囊壁CCK-AR mRNA表达。同时观察胆囊收缩率及结石率。结果:中药组胆囊壁厚度变薄,胆囊收缩功能改善,且均优于对照组(P<0.05);与模型组比较,治疗组豚鼠胆囊收缩率、CCK-AR mRNA表达增强(P<0.05):结论:利胆健脾法为主方药具有预防微创保胆取石术后结石复发的作用,其作用机制可能与调节胆囊壁CCK-AR mRNA表达有关。
Objective To discuss the methods of Cholagogic and Jianpi in the Prevention of Gallstone Recurrence after Stone Removement and this methods in mechanisms of CCK-A receptor of guinea pig.Method:In the part of clinical research,73 cases will be selected after minicholecy-stolithotomyremaning gallbladder patients were randomly divided into control group(34),Fangshi capsule group(34).The control group did not have any treatment after stone removement,Fangshi capsule group in the forth days after removal of the stones began taking Fangshi capsule,All patients observed for aperiod of 1 years(gallbladder wall and gallbladder contraction rate);In the part of Experimental study,90 guinea pig were randomly divided into control group(fed with normal diet,n=30),model group(fed with lithogenic diet,n=30) and treatment group(fed with lithogenic diet plus Fangshi capsule,n=30).After two-months feeding,the animals were sacrificed and sampled,The expression of CCK-A receptor mRNA in gallbladder tissue was subjected to RT-PCR assay,At the sametime, gallbladder contraction rate and the rates of gallstone formation in each group were observed.Results:Compared with the control group,Gallbladder wall of the Fangshi capsule group turned thin,the gallbladder contraction rate were improvement,(P＜0.05);Compared with the model group,increase of gallbladder contraction rate and the expression of CCK-A receptor mRNA (P＜0.05) were found in the treated group.Conclusion:Cholagogic and Jianpi can and prevent the recurrence of gallstone after mini-cholecysto-lithotomyremaning gallbladder,its mechanism is possibly correlated with Regulation of CCK-A receptor mRNA in gallbladder tissue.
Objective To discuss the methods of Cholagogic and Jianpi in the Prevention of Gallstone Recurrence after Stone Removement and this methods in mechanisms of CCK-A receptor of guinea pig.Method:In the part of clinical research,73 cases will be selected after minicholecy-stolithotomyremaning gallbladder patients were randomly divided into control group(34),Fangshi capsule group(34).The control group did not have any treatment after stone removement,Fangshi capsule group in the forth days after removal of the stones began taking Fangshi capsule,All patients observed for aperiod of 1 years(gallbladder wall and gallbladder contraction rate);In the part of Experimental study,90 guinea pig were randomly divided into control group(fed with normal diet,n=30),model group(fed with lithogenic diet,n=30) and treatment group(fed with lithogenic diet plus Fangshi capsule,n=30).After two-months feeding,the animals were sacrificed and sampled,The expression of CCK-A receptor mRNA in gallbladder tissue was subjected to RT-PCR assay,At the sametime, gallbladder contraction rate and the rates of gallstone formation in each group were observed.Results:Compared with the control group,Gallbladder wall of the Fangshi capsule group turned thin,the gallbladder contraction rate were improvement,(P＜0.05);Compared with the model group,increase of gallbladder contraction rate and the expression of CCK-A receptor mRNA (P＜0.05) were found in the treated group.Conclusion:Cholagogic and Jianpi can and prevent the recurrence of gallstone after mini-cholecysto-lithotomyremaning gallbladder,its mechanism is possibly correlated with Regulation of CCK-A receptor mRNA in gallbladder tissue.
引文
[1]中华外科学会胆道学组·我国胆石病十年来的变迁[J].中华外科杂志,1995;33(11):65.
[2]王炳生.胆囊结石的治疗要规范化[J].中华普通外科杂志,2000;15(10):638.
[3]刘禹翔,李健,郭绍举等.中医药对微创保胆取石后结石复发的预防作用[J].中医药临床杂志,2006;18(4):389-390.
[4]Chen M F,Wang M.A prospective study of the cholecystectocy on duodenogastric reflux in humans using 24 hour gastric hydrogenmonitoring.SGO,1992;175(7):52-56.
[5]Dionigi Lorusso M D,Giovanni Misciagna M D,Vito Mangmi S CD,etal.Duodenogastricreflux of bile acids,gasttrin and parietal cells,and gastric acid secretion before and 6 months after cholecystectomy.Am J Surg,1990;159(6):575-578.
[6]王广义,谭毓铨.医源性胆管损伤的临床进展.中国实用外科杂志,1999;19(8):497-499.
[7]李健,杨卓欣等.微创保胆内镜取石术加防石胶囊治疗胆囊结石的初步观察[J].中国中医药科技,2003;10(1):50-51.
[8]郭绍举,叶临湘,李健.中医药对微创保胆取石术后预防胆囊结石复发的研究[J].中国中医药科技,2005;9(1):30-31.
[9]张继红,杨可帧,韩本立.消炎痛、红霉素预防胆囊结石形成的实验研究[J],中国普通外科杂志,1998;7(3):129-132.
[10]Behar J,Lee KY,Thompson W,et al.Gallbladder contraction in pa-tientswith pigment,and cholesterol stones[J].Gastroenterology,1989;97(6):1479-1484.
[11]帅建,张圣道,韩天权等.胆囊结石病胆囊排空与胆囊收缩素受体基因表达关系的研究[J].中华外科杂志,1999;37(5):292.
[12]傅华群,蒋筱强,熊本京等.豚鼠体内生长抑素和血管活性肠肽在胆囊结石形成中的作用[J].中华实验外科杂志,2000;17(1):28-29.
[13]祝学光.浅谈我国胆道外科今后的发展方向.外科理论与实践,2003;8:89-91.
[14]Halpern Z,Dudley MA,Kibe A.Rapid vesicle formation aggregation in abnormal human biles[H].Gast ronterdogy,1986,90(4):875-885.
[15]Martin C,Carey MC.Pathogenesis of gallstones[J].Am J Surg,1993;165(2):410-419.
[16]张圣道,韩天权.胆石病的流行病学[M].当代胆道外科学.第1版。上海:上海科学技术文献出版社,1998,249.
[17]韩天权,张圣道,陈胜,等。用Logistic回归模型预测胆固醇结石易患人群[J]。中华消化杂志,1995,15(6):313-316.
[18]Glass CK,Witztum JL.Atherosclersis.The road ahead[J].Cell,2001,(104):503-516.
[19]费健,韩天权,蒋兆彦.胆囊结石病家系遗传特征的初步研究[J].肝胆胰外科杂志,2002:14:4-6.
[20]秦俭,韩天权,袁文涛等.胆囊结石病致病基因的定位研究.中华外科杂志,2006;44(7):485-487.
[21]Miyasaka K,Takata Y,Funakoshi A.Association of cholecystokinin A receptor gene polymorphism with cholelithiasis and the molecular mechanisms of this polymorphism[J].J Gastroenterol,2002;37(Suppl 14):102.
[22]韩天权.关于胆固醇结石成因机制及其预防飞研究动态[J].外科理论与实践,2001:6:188-190.
[23]Grundy SM.Highlight of the meeting on prevention of gallstones.Hepatology,1987;7:946-951.
[24]Jazrawi RP,Pazzip,Pet roni ML.Postgrandial gallbladder motor function:refilling and turnover of bile in health and in cholelithiasis[J].Gastroenterology,1995;109(2):582-2591.
[25]韩天权,蒋兆彦,陈胜等.胆固醇结石病高位人群预测的进步研究[J].中华医学杂志,2001;81(16):1010-1011.
[26]汪裕,王炳生.药物干预对胆囊结石体外震波碎石治疗后的抗复发临床观察[J].肝胆胰外科杂志,2000;12(4):187-188.
[27]李秀年,王杰方.辨证治疗胆系感染及胆石症56例临床观察[J].国医论坛,2001;16(3):27.
[28]叶韩锡.试论胆石症的辨治[J].吉林中医药,2001(1):13-14.
[29]赵履瑚.中医治疗胆石术后残余结石及结石再发病案报道[D].大理市中医,46,49.
[30]张红英.朱培庭治疗胆石病的经验[J].辽宁中医杂志,2002;29(9):523.
[31]赵世运,尚学瑞.辨证论治胆石症体会[J].光明中医,2003(3):18-19.
[32]朱培庭,朱世敏.实用中医胆道学[M].北京:人民卫生出版社,1999.279.
[33]Lammert F,Carey MC,Paigen B.Chromosomal organization of candicate genes involved in cholesterol gallstone formation:a murine gallstone map.Gastroenterology,2001,120:221-238.
[34]张宝善,内镜微创保胆取石术治疗胆囊结石[J].中国内镜杂志,8(7):1-4.
[35]曾俊群,姚松森,熊六林,等。经皮胆镜碎石取石术治疗胆囊结石295例疗效观 察[J].中华普通外科杂志,2000,15(7):420-422.
[36]Schoenfield LJ,Marks JW.Oral and contact dissolution of gallstones.AmJ surg,1993;165:427-430.
[37]Mcdermott VG,Arger p,Cope C.Gallstone recurrence and gallbladder fuction following percutaneous cholecystolithotomy,J Vasc Inertv Radiol,1994;5:473-478.
[38]蔡红.防石汤预防胆道结石复发30例[J]。福建中医药,2004,35(5):27.
[39]唐乾利,刘祖军,伍松合,等。大黄灵仙胶囊降低胆石症术后残石率及复发率疗效观察[J]。新中医,2002,34(6):17-19.
[40]李建兵.连钱草泡服为主治疗胆道结石术后复发[J].江西中医药,2004:35(255):21.
[41]范思行,庞国明.结石病诊疗常用书.北京:中国医药科技出版社,2000:3.
[42]朱培庭,张静哲,章学林.世纪之交的中医胆病学[J].中国中西医结合外科杂志,2001;7(1):8.
[43]陈胜,韩天权,蒋渝,等.胆囊结石患者胆囊动力学紊乱机制的研究[J].中华外科杂志,1998;36:14.
[44]郑培永,章学林等.胆囊结石病肝气郁结证与CCKAR和VIPR基因表达的相关性研究[J].中国中西医结合外科杂志2004;10(10):346-348.
[45]Lenon F,et,al.Effects of Histamin Receptor Stimu-Jation on Diseased Galibladder and Cystic Duct.Ca-Atrsentemlogy 1984:87:257-262.
[46]Xiao ZL,Chen Q,Amaral J,et al.CCK receptor dysfunctionin muscle membranes from human gallbladders with cholesterolstones.Am J Physiol 1999:276:1401-1407.
[2]王炳生.胆囊结石的治疗要规范化[J].中华普通外科杂志,2000;15(10):638.
[3]刘禹翔,李健,郭绍举等.中医药对微创保胆取石后结石复发的预防作用[J].中医药临床杂志,2006;18(4):389-390.
[4]Chen M F,Wang M.A prospective study of the cholecystectocy on duodenogastric reflux in humans using 24 hour gastric hydrogenmonitoring.SGO,1992;175(7):52-56.
[5]Dionigi Lorusso M D,Giovanni Misciagna M D,Vito Mangmi S CD,etal.Duodenogastricreflux of bile acids,gasttrin and parietal cells,and gastric acid secretion before and 6 months after cholecystectomy.Am J Surg,1990;159(6):575-578.
[6]王广义,谭毓铨.医源性胆管损伤的临床进展.中国实用外科杂志,1999;19(8):497-499.
[7]李健,杨卓欣等.微创保胆内镜取石术加防石胶囊治疗胆囊结石的初步观察[J].中国中医药科技,2003;10(1):50-51.
[8]郭绍举,叶临湘,李健.中医药对微创保胆取石术后预防胆囊结石复发的研究[J].中国中医药科技,2005;9(1):30-31.
[9]张继红,杨可帧,韩本立.消炎痛、红霉素预防胆囊结石形成的实验研究[J],中国普通外科杂志,1998;7(3):129-132.
[10]Behar J,Lee KY,Thompson W,et al.Gallbladder contraction in pa-tientswith pigment,and cholesterol stones[J].Gastroenterology,1989;97(6):1479-1484.
[11]帅建,张圣道,韩天权等.胆囊结石病胆囊排空与胆囊收缩素受体基因表达关系的研究[J].中华外科杂志,1999;37(5):292.
[12]傅华群,蒋筱强,熊本京等.豚鼠体内生长抑素和血管活性肠肽在胆囊结石形成中的作用[J].中华实验外科杂志,2000;17(1):28-29.
[13]祝学光.浅谈我国胆道外科今后的发展方向.外科理论与实践,2003;8:89-91.
[14]Halpern Z,Dudley MA,Kibe A.Rapid vesicle formation aggregation in abnormal human biles[H].Gast ronterdogy,1986,90(4):875-885.
[15]Martin C,Carey MC.Pathogenesis of gallstones[J].Am J Surg,1993;165(2):410-419.
[16]张圣道,韩天权.胆石病的流行病学[M].当代胆道外科学.第1版。上海:上海科学技术文献出版社,1998,249.
[17]韩天权,张圣道,陈胜,等。用Logistic回归模型预测胆固醇结石易患人群[J]。中华消化杂志,1995,15(6):313-316.
[18]Glass CK,Witztum JL.Atherosclersis.The road ahead[J].Cell,2001,(104):503-516.
[19]费健,韩天权,蒋兆彦.胆囊结石病家系遗传特征的初步研究[J].肝胆胰外科杂志,2002:14:4-6.
[20]秦俭,韩天权,袁文涛等.胆囊结石病致病基因的定位研究.中华外科杂志,2006;44(7):485-487.
[21]Miyasaka K,Takata Y,Funakoshi A.Association of cholecystokinin A receptor gene polymorphism with cholelithiasis and the molecular mechanisms of this polymorphism[J].J Gastroenterol,2002;37(Suppl 14):102.
[22]韩天权.关于胆固醇结石成因机制及其预防飞研究动态[J].外科理论与实践,2001:6:188-190.
[23]Grundy SM.Highlight of the meeting on prevention of gallstones.Hepatology,1987;7:946-951.
[24]Jazrawi RP,Pazzip,Pet roni ML.Postgrandial gallbladder motor function:refilling and turnover of bile in health and in cholelithiasis[J].Gastroenterology,1995;109(2):582-2591.
[25]韩天权,蒋兆彦,陈胜等.胆固醇结石病高位人群预测的进步研究[J].中华医学杂志,2001;81(16):1010-1011.
[26]汪裕,王炳生.药物干预对胆囊结石体外震波碎石治疗后的抗复发临床观察[J].肝胆胰外科杂志,2000;12(4):187-188.
[27]李秀年,王杰方.辨证治疗胆系感染及胆石症56例临床观察[J].国医论坛,2001;16(3):27.
[28]叶韩锡.试论胆石症的辨治[J].吉林中医药,2001(1):13-14.
[29]赵履瑚.中医治疗胆石术后残余结石及结石再发病案报道[D].大理市中医,46,49.
[30]张红英.朱培庭治疗胆石病的经验[J].辽宁中医杂志,2002;29(9):523.
[31]赵世运,尚学瑞.辨证论治胆石症体会[J].光明中医,2003(3):18-19.
[32]朱培庭,朱世敏.实用中医胆道学[M].北京:人民卫生出版社,1999.279.
[33]Lammert F,Carey MC,Paigen B.Chromosomal organization of candicate genes involved in cholesterol gallstone formation:a murine gallstone map.Gastroenterology,2001,120:221-238.
[34]张宝善,内镜微创保胆取石术治疗胆囊结石[J].中国内镜杂志,8(7):1-4.
[35]曾俊群,姚松森,熊六林,等。经皮胆镜碎石取石术治疗胆囊结石295例疗效观 察[J].中华普通外科杂志,2000,15(7):420-422.
[36]Schoenfield LJ,Marks JW.Oral and contact dissolution of gallstones.AmJ surg,1993;165:427-430.
[37]Mcdermott VG,Arger p,Cope C.Gallstone recurrence and gallbladder fuction following percutaneous cholecystolithotomy,J Vasc Inertv Radiol,1994;5:473-478.
[38]蔡红.防石汤预防胆道结石复发30例[J]。福建中医药,2004,35(5):27.
[39]唐乾利,刘祖军,伍松合,等。大黄灵仙胶囊降低胆石症术后残石率及复发率疗效观察[J]。新中医,2002,34(6):17-19.
[40]李建兵.连钱草泡服为主治疗胆道结石术后复发[J].江西中医药,2004:35(255):21.
[41]范思行,庞国明.结石病诊疗常用书.北京:中国医药科技出版社,2000:3.
[42]朱培庭,张静哲,章学林.世纪之交的中医胆病学[J].中国中西医结合外科杂志,2001;7(1):8.
[43]陈胜,韩天权,蒋渝,等.胆囊结石患者胆囊动力学紊乱机制的研究[J].中华外科杂志,1998;36:14.
[44]郑培永,章学林等.胆囊结石病肝气郁结证与CCKAR和VIPR基因表达的相关性研究[J].中国中西医结合外科杂志2004;10(10):346-348.
[45]Lenon F,et,al.Effects of Histamin Receptor Stimu-Jation on Diseased Galibladder and Cystic Duct.Ca-Atrsentemlogy 1984:87:257-262.
[46]Xiao ZL,Chen Q,Amaral J,et al.CCK receptor dysfunctionin muscle membranes from human gallbladders with cholesterolstones.Am J Physiol 1999:276:1401-1407.