摘要：
Objective To investigate precise and regulable animal model of benign bile duct strictures.Methods Mini pigs were divided into four groups as sham surgery group, conventional surgery group, small caliber group and large caliber group according to random number table, with 6 pigs in each group.For the small caliber group, outside diameter 3.0mm catheter were inserted into bile duct and partial sutured.For the large caliber group, outside diameter 6.0mm catheter were inserted into bile duct and partial sutured.Conventional surgery group were treated with 5-0 absorbable suture on distal bile duct and controlled stricture severity visually.For sham surgery group, bile duct were exposed without suture.Observe the general condition of four groups.Test liver function on 1st, 3rd, 7th, 14th, 21st and 28th day postoperative.Perform cholangiography on 30th day postoperative.All four groups were put to death to observe the histological changes of liver and bile duct.Results Liver function of sham surgery group showed no obvious change during observation.On 28th day postoperative, compared to conventional surgery group, the liver enzymes ALT, AST, γ-GT, ALP, bilirubin level of small caliber group elevated(P<0.05)and the liver enzymes ALT, AST, γ-GT, bilirubin level of large caliber group elevated(P<0.05),while ALP level lowered(P<0.05).Cholangiography showed bile duct stenosis of different degree on 6 pigs of small caliber group with average diameter 2.7mm (from 2mm to 4mm).As for large caliber group, 5 pigs showed stenosis with average diameter 5.5mm (from 5mm to 7mm).3 pigs of conventional surgery group showed no obvious bile duct stenosis.The 6 pigs of sham surgery group showed no bile duct stenosis.According to designed stenosis standard, the success rate of small caliber group and large caliber group are both higher than conventional surgery group.(P<0.05).30 days after surgery, all 6 pigs of small caliber group had postoperative intraperitoneal adhesion, hepatomegaly, obvious expansion of intrahepatic bile duct and gallbladder expanded by 4~5 times.5 pigs of large caliber group had hepatomegaly, slight dilation of intrahepatic bile duct, obvious expansion of gallbladder, clear choledochal edema, sutured tissue thickening and visible bile duct stenosis.HE staining with the small caliber group showed hepatocyte spotty degenerative necrosis, expanded cholestatic intrahepatic small bile duct, swelling hepatocyte and fibrous septa.HE staining with the large caliber group showed intrahepatic small bile duct slightly expanded and hepatocyte arranged basically normal.VG staining with the small caliber group showed excessive accumulaton of collagen fibers outside bile duct mucous cells, randomly and densely arranged and irregularly shaped.VG staining with the large caliber group showed increased collagen fibers in bile duct submucosa, densely and banded arranged.Conclusion This animal model of mini pig is an relatively ideal large animal model of biliary stricture with high surgical success rate and few postoperative complications.%目的 目前对胆管良性狭窄动物模型的研究尚少.探讨建立可调控胆管良性狭窄动物模型的方法. 方法 小型猪按随机数字表法分为假手术组、传统手术组、小口径组、大口径组,每组6只.其中小口径组以外径3.0mm导管置入胆总管后行部分缝扎;大口径组以外径6.0mm导管置入胆总管后行部分缝扎.传统手术组用5-0可吸收线对胆管下段部分缝扎,大致目视下控制狭窄程度.假手术组仅暴露胆管,未行缝扎处理.术后观察4组动物的一般状况;术后1,3,7,14,21,28d检测肝功能水平;术后30d行经胆囊胆道造影;造影术后所有猪均处死,解剖观察肝及胆管组织学变化情况. 结果 假手术组肝功能水平于整个观察期内未见明显变化.术后第28天,与传统手术组比较,小口径组肝酶检测指标ALT、AST、γ-GT 、ALP、胆红素水平升高(P<0.05);大口径组肝酶检测指标ALT、AST、γ-GT、胆红素水平升高(P<0.05),而大口径组较小口径组ALP水平降低(P<0.05).胆管造影示:小口径组6只猪胆管内明显可见不同程度狭窄,平均直径2.7mm(2~4mm);大口径组有5只猪可见明显管腔狭窄,狭窄段胆管直径为平均5.5mm(5~7mm),传统手术组有3只猪未见明显管腔狭窄,假手术组6只猪均无胆管狭窄形成.根据设计的狭窄形成标准,小口径组、大口径组狭窄成功率均高于传统手术组(P<0.05).术后30d小口径组6只猪均出现腹腔粘连,肝肿大,肝内胆管明显扩张,胆囊扩张可达原来5~6倍.大口径组5只猪肝肿大,肝内胆管轻度扩张,胆囊扩张明显,胆总管水肿明显,缝扎部位组织增厚,胆管可见狭窄.HE染色见小口径组肝细胞点状变性坏死,肝内小胆管呈扩张淤胆状态,肝细胞肿胀,出现纤维隔;大口径组可见肝内小胆管呈轻度扩张状态,肝细胞排列基本正常.VG染色见小口径组胆管黏膜细胞外胶原纤维沉积过度,排列杂乱而较密,形状不规则.大口径组胆管黏膜下胶原纤维增多,排列致密呈条带状. 结论 此模型具有手术成功率高,并发症少等优点,是较为理想的胆管良性狭窄大动物模型.
