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厚朴酚治疗重症急性胰腺炎大鼠模型并发急性肺损伤的作用机制
Mechanism of action of magnolol in the treatment of acute lung injury in a rat model of severe acute pancreatitis
文章发布日期:2020年11月13日  来源:  作者:王燕,齐文杰,曾亚薇,等  点击次数:2682次  下载次数:26次

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【摘要】:目的 从厚朴酚功能性阻断肠淋巴循环研究厚朴酚对重症急性胰腺炎(SAP)并发急性肺损伤大鼠模型的治疗作用。方法 将健康雄性SD大鼠30只随机分为假手术组、SAP组、厚朴酚治疗组,每组各10只。假手术组开腹翻动胰腺后关腹。SAP组采用逆行胰胆管注射3.75%的牛磺胆酸钠建立SAP大鼠模型;厚朴酚治疗组造模前15 min经阴茎静脉注射厚朴酚0.2 mg/kg。比较肺和肠组织病理变化并进行病理学评分;比较血清、淋巴液、肺及肠组织匀浆中D-乳酸(DLA),二胺氧化酶(DAO)、高迁移率族蛋白1(HMGB1)、晚期糖基化终产物受体(RAGE)、IL-1β、IL-8、IL-10、TNFα水平及淋巴液中Toll样受体4(TLR4)水平。符合正态分布的计量资料组间比较采用方差分析,不符合正态分布的计量资料组间比较采用Kruskal-Wallis H检验。结果 SAP组大鼠肺间质可见充血、水肿、炎细胞浸润、出血;厚朴酚治疗组肺组织轻度出血和炎细胞浸润,病变程度较SAP组轻。厚朴酚治疗组大鼠血清中DAO、DLA、IL-1β、IL-8、TNFα、HMGB1、RAGE均低于SAP组(P值均<0.05);假手术组大鼠血清中DAO、DLA、IL-1β、IL-8、TNFα、HMGB1、RAGE均低于SAP组(P值均<0.05)。厚朴酚治疗组大鼠淋巴液中DAO、DLA、IL-1β、IL-8、TNFα、HMGB1、RAGE均低于SAP组(P值均<0.05);假手术组大鼠淋巴液中DAO、DLA、IL-1β、IL-8、TNFα、HMGB1、RAGE均低于SAP组(P值均<0.05)。厚朴酚治疗组大鼠肺组织中IL-1β、IL-8、TNFα、HMGB1、RAGE均低于SAP组(P值均<0.05);假手术组大鼠肺组织中IL-1β、IL-8、TNFα、HMGB1、RAGE均低于SAP组(P值均<0.05)。厚朴酚治疗组大鼠肠组织中IL-1β、IL-8、TNFα、HMGB1、RAGE均低于SAP组(P值均<0.05);假手术组大鼠肠组织中IL-1β、IL-8、TNFα、HMGB1、RAGE均低于SAP组(P值均<0.05)。厚朴酚治疗组及假手术组大鼠淋巴液中TLR4蛋白较SAP组表达均减少(P值均<0.05)。结论 厚朴酚能够改善肠屏障功能,通过功能性阻断肠淋巴循环,降低炎症因子水平,抑制HMGB1-TLR4/NF-κB信号转导通路,减轻SAP肺损伤。
【Abstract】:Objective To investigate the therapeutic effect of magnolol on severe acute pancreatitis (SAP) with acute lung injury from the aspect of the functional block of intestinal lymphatic circulation by magnolol. Methods A total of 30 healthy male Sprague-Dawley rats were randomly divided into sham-operation group, SAP group, and magnolol treatment group, with 10 rats in each group. The rats in the sham-operation group were given laparotomy to flip the pancreas, followed by abdominal closure; the rats in the SAP group were given retrograde pancreaticobiliary injection of 3.75% sodium taurocholate to establish a rat model of SAP; the rats in the magnolol treatment group were given injection of magnolol 0.2 mg/kg via the penile vein at 15 minutes before modeling. The three groups were compared in terms of pathological changes of the lung and the intestine, pathological score, the levels of D-lactic acid (DLA), diamine oxidase (DAO), high-mobility group box 1 (HMGB1), receptor for advanced glycation end products (RAGE), interleukin-1β (IL-1β), interleukin-8 (IL-8), interleukin-10 (IL-10), and tumor necrosis factor-α (TNFα) in serum, lymphatic fluid, and tissue homogenate of the lung and the intestine, and the level of Toll-like receptor 4 (TLR4) in lymphatic fluid. An analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups. Results The SAP group had congestion, edema, inflammatory cell infiltration, and bleeding in the pulmonary interstitium, and the magnolol treatment group had mild bleeding and inflammatory cell infiltration in the pulmonary interstitium, with a significantly lower degree than the SAP group. Compared with the SAP group,the magnolol treatment group had significantly lower serum levels of DAO,DLA,IL-1β,IL-8,TNFα,HMGB1, and RAGE(all P<0.05)and significantly lower levels of DAO,DLA,IL-1β,IL-8,TNFα,HMGB1, and RAGE in the lymphatic fluid(all P<0.05).Compared with the SAP group,the sham-operation group had significantly lower serum levels of DAO,DLA,IL-1β,IL-8,TNFα,HMGB1, and RAGE(all P<0.05)and significantly lower levels of DAO,DLA,IL-1β,IL-8,TNFα,HMGB1, and RAGE in the lymphatic fluid(all P<0.05). Compared with the SAP group, the magnolol treatment group had significantly lower levels of IL-1β, IL-8, TNFα, HMGB1, and RAGE in lung tissue (all P<0.05) and intestinal tissue (all P<0.05). Compared with the SAP group, the sham-operation group had significantly lower levels of IL-1β,IL-8,TNFα,HMGB1, and RAGE in lung tissue (all P<0.05) and intestinal tissue (all P<0.05). Compared with the SAP group,the magnolol treatment group and sham-operation group had a significant reduction in the protein expression of TLR4 in the lymphatic fluid (all P<0.05). Conclusion Magnolol can improve intestinal barrier function and alleviate lung injury in SAP by blocking intestinal lymphatic circulation, reducing the levels of inflammatory factors, and inhibiting the HMGB1-TLR4/NF-κB signal transduction pathway.
【关键字】:胰腺炎,急性坏死性; 急性肺损伤; 厚朴酚; 治疗学
【Key words】:pancreatitis,acute necrotizing; acute lung injury; MAGNOLOL; therapeutics
【引证本文】:WANG Y, QI WJ, ZENG YW, et al. Mechanism of action of magnolol in the treatment of acute lung injury in a rat model of severe acute pancreatitis[J]. J Clin Hepatol, 2020, 36(12): 2782-2787. (in Chinese)
王燕, 齐文杰, 曾亚薇, 等. 厚朴酚治疗重症急性胰腺炎大鼠模型并发急性肺损伤的作用机制[J]. 临床肝胆病杂志, 2020, 36(12): 2782-2787.

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