Department of Biliary Surgery, Sichuan University, West China Hospital, No. 37 Guo Xue Xiang, 610041 Chengdu, Sichuan, China; Laboratory of Pathology, Sichuan University, West China Hospital, 610041 Chengdu, China.
Laboratory of Pathology, Sichuan University, West China Hospital, 610041 Chengdu, China.
Clin Res Hepatol Gastroenterol. 2020 Jun;44(3):356-367. doi: 10.1016/j.clinre.2019.07.008. Epub 2019 Aug 13.
The gram-negative bacteria secreted endotoxin, Lipopolysaccharide (LPS), plays important roles in the formation and recurrence of hepatolithiasis and chronic biliary inflammation in patients of Southeast Asia. We aimed to elucidate the anti-inflammatory effect and mechanism of local antibiotics irrigation on chronic proliferative cholangitis (CPC) and hepatolithiasis.
Escherichia coli was injected into rabbit bile ducts to induce CPC. Rabbits were divided into sham operation (SO), povidone-iodine, Metronidazole plus chlorhexidine, ofloxacin, furacillin, Neosporin® G.U., and CPC groups. Local irrigation was performed for 28 days after CPC was established. Residual E. coli and LPS, and the expression of MCP-1, CD14, COX-2, VEGF, IL-6, NF-κB, TNF-α, Fas, TGF-β1, α-SMA, Collagen-I, β-glucuronidase, PKC, C-myc, and Mucin 5AC were assessed in bile duct tissues.
The residual E. coli and LPS, and expression of MCP-1, CD14, COX-2, IL-6, NF-κB, TNF-α, Fas, TGF-β1, α-SMA, β-glucuronidase, PKC, C-myc, and Mucin 5AC in the SO, povidone-iodine, Metronidazole plus chlorhexidine, ofloxacin, and Neosporin® G.U. groups were significantly lower than those in the furacillin and CPC groups (P<0.05). VEGF and Collagen-I levels in the SO, povidone-iodine, metronidazole plus chlorhexidine, and ofloxacin groups were significantly lower than those in the furacillin, Neosporin® G.U., and CPC groups (P<0.05).
LPS affects the pathophysiology of E. coli caused chronic proliferative cholangitis and hepatolithiasis recurrence. Local antibiotics irrigation could prevent chronic proliferative cholangitis and stones formation by decreasing LPS-induced proinflammatory and profibrotic cytokines release. Povidone iodine, metronidazole plus chlorhexidine, and ofloxacin were more effective than Neosporin® G.U. and furacillin.
革兰氏阴性菌分泌的内毒素脂多糖（LPS）在东南亚患者的胆石病和慢性胆管炎症的形成和复发中起重要作用。我们旨在阐明局部抗生素灌洗对慢性增生性胆管炎（CPC）和胆石病的抗炎作用及其机制。
将大肠杆菌注入兔胆管以诱导 CPC。兔子分为假手术（SO）、聚维酮碘、甲硝唑加氯己定、氧氟沙星、呋喃西林、新霉素 G.U. 和 CPC 组。在建立 CPC 后 28 天进行局部灌洗。评估胆管组织中残留的 E. coli 和 LPS 以及 MCP-1、CD14、COX-2、VEGF、IL-6、NF-κB、TNF-α、Fas、TGF-β1、α-SMA、Collagen-I、β-葡萄糖醛酸酶、PKC、C-myc 和 Mucin 5AC 的表达。
SO、聚维酮碘、甲硝唑加氯己定、氧氟沙星和新霉素 G.U. 组的残留 E. coli 和 LPS 以及 MCP-1、CD14、COX-2、IL-6、NF-κB、TNF-α、Fas、TGF-β1、α-SMA、β-葡萄糖醛酸酶、PKC、C-myc 和 Mucin 5AC 的表达明显低于呋喃西林和 CPC 组（P<0.05）。SO、聚维酮碘、甲硝唑加氯己定和氧氟沙星组的 VEGF 和 Collagen-I 水平明显低于呋喃西林、新霉素 G.U. 和 CPC 组（P<0.05）。
LPS 影响大肠埃希菌引起的慢性增生性胆管炎和胆石病复发的病理生理学。局部抗生素灌洗可通过减少 LPS 诱导的促炎和促纤维化细胞因子释放来预防慢性增生性胆管炎和结石形成。聚维酮碘、甲硝唑加氯己定和氧氟沙星比新霉素 G.U. 和呋喃西林更有效。
