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首页> 外文期刊>International journal of colorectal disease. >Nonselective matrix metalloproteinase but not tumor necrosis factor-alpha inhibition effectively preserves the early critical colon anastomotic integrity.
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Nonselective matrix metalloproteinase but not tumor necrosis factor-alpha inhibition effectively preserves the early critical colon anastomotic integrity.

机译：非选择性基质金属蛋白酶而不是肿瘤坏死因子-α抑制有效保留早期关键结肠吻合的完整性。

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BACKGROUND: Increased matrix metalloproteinase (MMP) activity has been implicated in the pathogenesis of colorectal anastomotic leakage. Tumor necrosis factor-alpha (TNF-alpha) induces MMPs and may influence anastomosis repair. METHODS: We assessed the efficacies of the nonselective hydroxamate MMP inhibitor GM6001, the selective hydroxamate MMP inhibitor AG3340 and a TNF-alpha antagonist with respect to anastomotic breaking strength of left-sided colon anastomoses in male Sprague-Dawley rats. RESULTS: Systemic GM6001 treatment effectively blocked MMP activity and maintained the initial breaking strength day 0 of the anastomoses when administered subcutaneously as daily depositions (100 mg/kg) or continuously (10 mg/kg/day). In contrast, the anastomotic biomechanic strength was lowered by 55% (p < 0.001) in vehicle-treated rats on postoperative day 3. GM6001 treatment increased breaking strength by 88% (p < 0.0005) compared with vehicle-treated rats day 3 and reduced (p = 0.003) the occurrence of spontaneous anastomotic dehiscence. Histologically, the anastomotic wound was narrower (p < 0.05) in the longitudinal direction in GM6001-treated animals whereas GM6001 had no significant effect on inflammatory cell infiltration or epithelialization. AG3340 (10 mg/kg) increased (p < 0.012) breaking strength by 47% compared with vehicle on day 3 but did not significantly prevent the reduction of the initial breaking strength on day 0. Although the increased TNF-alpha levels in the wound were attenuated, the anastomotic breaking strength was not improved (p = 0.62) by the TNF-alpha (10 mg/kg) inhibitor given systemically. CONCLUSIONS: Pharmacological nonselective MMP inhibition ought to be explored as a prophylactic regimen to reduce anastomotic complications following colorectal resection. The involvement of TNF-alpha was insignificant in anastomotic wound healing in an experimental model.
机译：背景：增加的基质金属蛋白酶（MMP）活性已被认为与大肠吻合口漏的发病机制有关。肿瘤坏死因子-α（TNF-alpha）诱导MMPs，并可能影响吻合修复。方法：我们评估了非选择性异羟肟酸酯MMP抑制剂GM6001，选择性异羟肟酸酯MMP抑制剂AG3340和TNF-α拮抗剂对雄性Sprague-Dawley大鼠左侧结肠吻合口吻合破坏强度的疗效。结果：当每日皮下注射（100 mg / kg）或连续（10 mg / kg / day）皮下给药时，全身性GM6001处理有效地阻断了MMP活性并维持了吻合口的初始断裂强度第0天。相反，在术后第3天，用赋形剂处理的大鼠的吻合生物力学强度降低了55％（p <0.001）。与用赋形剂处理的大鼠第3天相比，GM6001处理的断裂强度提高了88％（p <0.0005），并且降低了（p = 0.003）发生自发吻合口裂。从组织学上看，GM6001处理的动物的纵向吻合伤口较窄（p <0.05），而GM6001对炎性细胞浸润或上皮形成没有明显影响。与第3天的载剂相比，AG3340（10 mg / kg）的抗张强度提高了（p <0.012）47％，但并未显着阻止第0天的初始抗张强度的降低。尽管伤口中的TNF-alpha水平升高全身给予TNF-α（10 mg / kg）抑制剂后，其吻合破坏强度未得到改善（p = 0.62）。结论：应探索药理学上非选择性的MMP抑制作用作为减少大肠切除术后吻合口并发症的预防方案。在实验模型中，TNF-α的参与对吻合口伤口愈合没有影响。

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