本文選題：干酪乳桿菌代田株　切入點：利福平　出處：《青島大學》2017年碩士論文

【摘要】：目的利福平(RFP)和異煙肼(INH)是WHO推薦的一線抗結核治療藥物,也是我國急性藥物性肝損傷的重要病因。本研究通過補充干酪乳桿菌代田株(Lactobacillus casei strain Shirota,LcS),觀察其對利福平和異煙肼致大鼠肝損傷的保護作用及對腸道菌群的影響。方法72只雄性SD大鼠,隨機分為6組;正常對照組,藥物組(誘發(fā)肝損傷),藥物+LcS低劑量組(LcS低)、藥物+LcS中劑量組(LcS中)、藥物+LcS高劑量組(LcS高),藥物+雙環(huán)醇組(作為陽性對照),每組12只。藥物組、LcS低、中、高劑量組及雙環(huán)醇組大鼠每只每天灌胃異煙肼(50mg/kg)和利福平(50 mg/kg),正常對照組大鼠每只灌胃等體積的生理鹽水;2h后LcS低、中、高劑量組大鼠每只分別灌胃10×108CFU/kg、20×108CFU/kg、40×108CFU/kg益生菌,雙環(huán)醇組大鼠每只灌胃7.5mg/kg雙環(huán)醇,每次灌胃20ml/kg,每天1次,連續(xù)給藥28d。主要檢測肝臟系數(shù),全自動生化分析儀分析大鼠血清谷丙轉氨酶(ALT)、谷草轉氨酶(AST)、堿性磷酸酶(ALP)、血清總膽汁酸(TBA)、總膽紅素(TBIL)、直接膽紅素(DBIL)、間接膽紅素(IBIL)水平,羥胺法檢測肝勻漿超氧化物歧化酶(SOD)活性、硫代巴比妥酸法檢測丙二醛(MDA)含量,PCR法檢測大鼠糞便中乳酸桿菌、雙歧桿菌、大腸桿菌和糞腸球菌含量等。結果利福平和異煙肼(50mg/kg·d)給藥28d可使大鼠氧化應激水平、肝功能和腸道菌群出現(xiàn)異常,藥物組大鼠肝組織SOD和MDA分別達到72.51U/mgprot和4.52U/mgprot,血清ALT和ALP分別達到65.45U/L和322.79U/L。補充LcS后,氧化應激水平分析顯示,與藥物組相比,LcS低、中、高劑量組和雙環(huán)醇組大鼠肝組織MDA含量顯著下降,分別降低了34.96%、37.61%、42.04%和36.28%;SOD活性顯著增強,分別升高了16.67%、18.99%、24.64%和27.78%(P均0.05)。肝功能水平分析顯示,與藥物組相比,LcS高劑量組大鼠血清ALT、ALP水平分別降低了16.3%和14.4%;LcS低、中、高劑量組大鼠的血清TBA水平分別降低了26.0%、39.4%和42.1%;LcS中、高劑量組大鼠的血清DBIL和IBIL水平也明顯降低,其中DBIL分別降低了22.6%和37.9%,IBIL分別降低了13%和15.4%(P均0.05)。與藥物組相比,雙環(huán)醇組大鼠的血清TBA、TBIL、DBIL、IBIL水平分別降低了29.4%、19.1%、24.7%和18.4%(P均0.05)。腸道菌群分析結果顯示,與藥物組相比,LcS低、中、高劑量組大鼠糞便中雙歧桿菌和乳酸桿菌的數(shù)量明顯升高(P均0.05),糞腸球菌和大腸桿菌的數(shù)量有明顯降低(P均0.05)。結論利福平和異煙肼合用可引起大鼠肝損傷,補充益生菌能有效地減輕抗結核藥物性肝損傷,并且可改善腸道菌群紊亂。
[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.緇撴灉鍒╃騫沖拰寮傜儫鑲，

本文編號：1702530