干酪乳杆菌对利福平和异烟肼联用所致大鼠肝损伤的保护作用

Protective effects of Lactobacillus casei on liver injury induced by rifampicin combined with isoniazid in rats

目的观察干酪乳杆菌代田株（Lactobacillus casei strain Shirota，LcS）对RFP和INH联合用药所致大鼠肝损伤的保护作用。方法将72只无特定病原体（SPF）级雄性SD大鼠，按随机数字表法分为：正常对照组，模型组，LcS低、中、高剂量组，双环醇组，每组12只。模型组，LcS低、中、高剂量组及双环醇组大鼠每天灌胃RFP（50mg／kg）和INH（50mg／kg），2h后LcS低、中、高剂量组大鼠分别灌胃10×10^8、20×10^8、40×10^8菌落形成单位（CFU）／kg的LcS，持续28d。正常对照组大鼠灌胃0．9％生理盐水（20ml／kg），双环醇组大鼠灌胃7．5mg／kg双环醇，每天1次，持续28d。检测大鼠肝脏指数、肝匀浆超氧化物歧化酶（SOD）活性和丙二醛（MDA）含量、血清谷氨酸氨基转氨酶（ALT）、天冬氨酸氨基转氨酶（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）等，并进行比较。结果RFP和INH给药28d后，模型组大鼠肝脏系数升高到（3．14±0．15）％，肝匀浆中MDA和SOD分别达到（4．52±0．52）nmol／mg蛋白和（72．51±11．05）U／mg蛋白；血清ALT和ALP分别达到（65．45±20．10）U／L和（322．79±61．73）U／L，TBA、TBIL、DBIL、IBIL分别达到（91．34±16．93）μmol／L、（7．82±2．53）μmol／L、（4．70±1．29）／μmol／L和（3．69±0．54）μmol／L。LcS补充后，与模型组相比，LcS高剂量组大鼠肝脏系数降低到（2．88±0．12）％；LcS低、中、高剂量组大鼠MDA含量明显下降，分别达到（2．94±0．48）nmol／mg蛋白、（2．82±0．36）nmol／mg蛋白和（2．62±0．28）nmol／mg蛋白；SOD活性明显增强，分别达到（84．60±8．50）U／mg蛋白、（86．28±5．52）U／mg蛋白和（2．62±0．28）U／mg蛋白。与模型组相比，LcS高剂量组的ALT、ALP均降低，分别为（49．92±15．32）U／L和（280．70±54．32）U／L；LcS低、中、高剂量组的TBA水平分别降低到（67．63±18．95）μmol／L、（55．32士19．17）μmlol／L和（52．92±23．00）μmol／L；LcS中、高剂量组的DBIL和IBIL水平也明显降低，其中DBIL分别降低到（3．64±1．68）μmol／L和（2．92±0．86）μmol／L，IBIL分别降低到（3．21±0．22）μmol／L和（3．12±0．42）μmol／L，差异均有统计学意义（P值均〈0．05）。与模型组相比，双环醇组大鼠的血清TBA、TBIL、DBIL、IBIL水平分别降低到（64．49±22．41）μmol／L、（6．33±1．46）μmol／L、（3．54土1．21）μmol／L和（3．01±0．36）μmol／L，差异均有统计学意义（P值均〈0．05）。结论干酪乳杆菌能减轻RFP和INH联合所致的大鼠肝损伤。

Objective To explore the protective effect of Lactobacillus casei strain Shirota （LcS） on liver injury induced by rifampin （RFP） combined with isoniazid （INH） in rats. Methods Seventy-two specific pathogen free （SPF） male SD rats were randomly divided into 6 groups including normal control group, model group, low- dose, mid-dose and high-close LcS groups, and bieyclol group （each n：12）. Rats in model group, low-dose, mid dose, high-dose LcS groups and bicyclol group were given by gavage with INH （50 mg/kg） and RFP （50 mg/kg） once a day, and two hours later, low dose, mid-dose, high-dose LcS groups were given by gavage LcS of 10 × 10^8 CFU/kg, 20× 10^8 CFU/kg and 40× 10^8 CFU/kg, respevtivel; the normal control group were given by gavage with physiological saline （20 ml/kg） once a day, and the bicyclol group were given by gavage with bicylol （7.5 mg/kg） once a day. Total duration of the 6 groups was all 28 days. The liver index, superoxidedismutase （SOD）, malondi- aldehyde （MDA）, alanine aminotransferase （ALT）, aspartate transaminase （AST）, alkaline phosphatase （ALP）, total biliary acid （TBA）, total bilirubin （TBIL）, direct bilirubin （DBIL） and indirect bilirubin （IBIL） wre tested and compared. Results When RFP and INH were given by gavage for 28 days, in model group, the liver index increased to （3. 14 ± 0. 15） %, the contents of MDA and SOD in model group were （4. 52±0. 52） nmol/mgprot and （72.51±11.05） U/mgprot, the ALT and ALP were （65.45±20.10） U/L and （322.79±61.73） U/L, the contents of TBA, TBIL, DBIL and IBIL were （91.34±16.93）μmol/L, （7.82±2. 53）μmol/L, （4. 70±1.29）mol/L and （3.69±0. 54）mol/L, respectively. After supplement of LcS, the liver index of LcS high-dose group decreased to （2.88 ± 0. 12） % the content of MDA in the probiotics groups decreased significantly by （2. 94±0. 48） nmol/mgprot, （2.82±0.36） nmol/mgprot and （2.62±0.28） nmol/mgprot and the content of SOD in the prohiotics groups significantly increased to （84. 60±8.50） U/mgprot, （86.28±5.52） U/mgprot and （2.62±0.28） U/mgprot. Compared with the model group, the ALT and ALP of high-dose probiotics group decreased to （49.92± 15.32） U/L and （280.70±54.32） U/L, respectively, the levels of TBA in low-dose, mid-dose and high-dose probiotics groups were also significantly decreased to （67. 632± 18.95） mol/L, （55. 322± 19.17） mol/L and （52.92 ± 23.00） mol/LL, respectively, the DBIL of middle- and high-dose probiotics groups were significantly decreased to （3.64 ±1.68）μmol/L and （2.92±0.86）/μmol/L, and the IBIL were significantly decreased to （3.21!0. 22）μmol/L and （3.12±0. 42） μmol/L, differences were statistically significant （P〈0.05）. Compared to model group, levels of TBA, TBIL, DBIL and IBIL in bicyclol group were reduced to （64.49 ± 22.41） μmol/L, （6.33 ±1.46） μmol/L, （3.54±1.21） μmol/L and （3.01 ±0.36） μmol/L, respectively. Conclusion LcS could reduce the liver injury induced by RFP combined with INH in rats.