益生菌（L casei）对利福平联合应用异烟肼致大鼠肝损伤及肠道菌群影响的研究

发布时间：2018-04-02 23:12

  本文选题：干酪乳杆菌代田株　切入点：利福平　出处：《青岛大学》2017年硕士论文

【摘要】：目的利福平(RFP)和异烟肼(INH)是WHO推荐的一线抗结核治疗药物,也是我国急性药物性肝损伤的重要病因。本研究通过补充干酪乳杆菌代田株(Lactobacillus casei strain Shirota,LcS),观察其对利福平和异烟肼致大鼠肝损伤的保护作用及对肠道菌群的影响。方法72只雄性SD大鼠,随机分为6组;正常对照组,药物组(诱发肝损伤),药物+LcS低剂量组(LcS低)、药物+LcS中剂量组(LcS中)、药物+LcS高剂量组(LcS高),药物+双环醇组(作为阳性对照),每组12只。药物组、LcS低、中、高剂量组及双环醇组大鼠每只每天灌胃异烟肼(50mg/kg)和利福平(50 mg/kg),正常对照组大鼠每只灌胃等体积的生理盐水;2h后LcS低、中、高剂量组大鼠每只分别灌胃10×108CFU/kg、20×108CFU/kg、40×108CFU/kg益生菌,双环醇组大鼠每只灌胃7.5mg/kg双环醇,每次灌胃20ml/kg,每天1次,连续给药28d。主要检测肝脏系数,全自动生化分析仪分析大鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、血清总胆汁酸(TBA)、总胆红素(TBIL)、直接胆红素(DBIL)、间接胆红素(IBIL)水平,羟胺法检测肝匀浆超氧化物歧化酶(SOD)活性、硫代巴比妥酸法检测丙二醛(MDA)含量,PCR法检测大鼠粪便中乳酸杆菌、双歧杆菌、大肠杆菌和粪肠球菌含量等。结果利福平和异烟肼(50mg/kg·d)给药28d可使大鼠氧化应激水平、肝功能和肠道菌群出现异常,药物组大鼠肝组织SOD和MDA分别达到72.51U/mgprot和4.52U/mgprot,血清ALT和ALP分别达到65.45U/L和322.79U/L。补充LcS后,氧化应激水平分析显示,与药物组相比,LcS低、中、高剂量组和双环醇组大鼠肝组织MDA含量显著下降,分别降低了34.96%、37.61%、42.04%和36.28%;SOD活性显著增强,分别升高了16.67%、18.99%、24.64%和27.78%(P均0.05)。肝功能水平分析显示,与药物组相比,LcS高剂量组大鼠血清ALT、ALP水平分别降低了16.3%和14.4%;LcS低、中、高剂量组大鼠的血清TBA水平分别降低了26.0%、39.4%和42.1%;LcS中、高剂量组大鼠的血清DBIL和IBIL水平也明显降低,其中DBIL分别降低了22.6%和37.9%,IBIL分别降低了13%和15.4%(P均0.05)。与药物组相比,双环醇组大鼠的血清TBA、TBIL、DBIL、IBIL水平分别降低了29.4%、19.1%、24.7%和18.4%(P均0.05)。肠道菌群分析结果显示,与药物组相比,LcS低、中、高剂量组大鼠粪便中双歧杆菌和乳酸杆菌的数量明显升高(P均0.05),粪肠球菌和大肠杆菌的数量有明显降低(P均0.05)。结论利福平和异烟肼合用可引起大鼠肝损伤,补充益生菌能有效地减轻抗结核药物性肝损伤,并且可改善肠道菌群紊乱。
[Abstract]:Objective Rifampicin (RFP) and isoniazid (INH) are first-line antituberculous drugs recommended by WHO and an important cause of acute drug-induced liver injury in China.In this study, the protective effect of Lactobacillus casei strain Shirotatathion on liver injury induced by rifampicin and isoniazid in rats and its effect on intestinal flora were observed.Methods Seventy-two male Sprague-Dawley rats were randomly divided into 6 groups: normal control group, normal control group,The drug group (induced liver injury), the low dose group of drug LcS, the middle dose group of drug LcS, the high dose group of drug LcS, the high dose group of drug LcS, and the group of drug dicyclic alcohol (12 rats in each group).Rats in the high dose group were given 10 脳 108 CFU / kg and 20 脳 10 8 CFU / kg respectively with 40 脳 108CFU/kg probiotics, and each rat in the bicyclic alcohol group was given 7.5mg/kg bicyclic alcohol 20 ml / kg once a day for 28 days.The liver coefficient was detected. The serum levels of alanine aminotransferase (alt), alanine aminotransferase (alt), alkaline phosphatase (ALP), total bile acid (TBA), total bilirubin (TBILN), direct bilirubin (DBIL) and indirect bilirubin (IBIL) were analyzed by automatic biochemical analyzer.The activity of superoxide dismutase (SOD) in liver homogenate was detected by hydroxylamine method, and the content of malondialdehyde (MDA) in rat faeces by thiobarbituric acid method. The contents of lactobacillus, bifidobacterium, Escherichia coli and Enterococcus faecalis were detected by PCR.缁撴灉鍒╃�忓钩鍜屽紓鐑熻偅�

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