红杉醇对2型糖尿病大鼠肝脏炎症损伤的保护作用
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摘要
目的:观察红杉醇对2型糖尿病大鼠肝脏炎症损伤的保护作用及其机制。方法:制备高脂高糖饮食加腹腔注射小剂量链脲佐菌素(streptozotocin,STZ)诱导的糖尿病大鼠肝脏炎症损伤模型。取造模成功大鼠35只,每天灌服不同剂量红杉醇(12.5、25和50 mg/kg)1次,连续6周。末次给药后取血,测空腹血糖、血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和白蛋白(ALB);取肝脏称湿重,计算肝脏指数,测定肝组织C反应蛋白(CRP)、肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)含量,real-time PCR检测肝脏TNF-αmRNA含量,HE染色观察病理变化。结果:模型组大鼠红杉醇治疗6周后,空腹血糖显著下降;肝功能改善,血清ALT和AST活性明显降低,ALB含量明显增加;CRP含量明显减少;肝组织中TNF-αmRNA和TNF-α、IL-6含量明显降低;肝脏指数下降,光镜下可见肝细胞病理改变(水肿、点状或灶状坏死及炎症细胞浸润)均有不同程度的改善。结论:红杉醇对2型糖尿病肝脏炎症损伤具有保护作用,其机制可能与其抑制TNF-α和IL-6有关。
AIM: To investigate the possible protective effect of sequoyitol on type 2 diabetic rats with liver inflammatory lesions.METHODS: Type 2 diabetic rats were induced by feeding high-fat/high-sugar diet and injecting with a low dose of streptozotocin.Sequoyitol at doses of 12.5,25 and 50 mg·kg-1·d-1 was orally administered in the model rats.At the end of the experiment,the rats were sacrificed.Serum levels of fasting blood glucose,alanine aminotransferase(ALT),aspartate aminotransferase(AST) and albumin(ALB) were determined.Liver wet was recorded and liver index was calculated.The levels of C-reactive protein(CRP),tumor necrosis factor α(TNF-α) and interleukin 6(IL-6) in the liver tissues were also measured.Real-time PCR was used to determine the mRNA expression of TNF-α.In addition,the pathological changes of the liver were observed with HE staining.RESULTS: Compared with the model rats,treatment with sequoyitol obviously decreased the levels of fasting blood glucose,ALT,AST,ALB,CRP,TNF-α and IL-6,reduced the liver index,down-regulated the mRNA expression of TNF-α in the liver,and ameliorated the pathologic changes of the liver.CONCLUSION: Sequoyitol attenuates liver lesions in type 2 diabetic rats through down-regulation of TNF-α and IL-6 expression.
AIM: To investigate the possible protective effect of sequoyitol on type 2 diabetic rats with liver inflammatory lesions.METHODS: Type 2 diabetic rats were induced by feeding high-fat/high-sugar diet and injecting with a low dose of streptozotocin.Sequoyitol at doses of 12.5,25 and 50 mg·kg-1·d-1 was orally administered in the model rats.At the end of the experiment,the rats were sacrificed.Serum levels of fasting blood glucose,alanine aminotransferase(ALT),aspartate aminotransferase(AST) and albumin(ALB) were determined.Liver wet was recorded and liver index was calculated.The levels of C-reactive protein(CRP),tumor necrosis factor α(TNF-α) and interleukin 6(IL-6) in the liver tissues were also measured.Real-time PCR was used to determine the mRNA expression of TNF-α.In addition,the pathological changes of the liver were observed with HE staining.RESULTS: Compared with the model rats,treatment with sequoyitol obviously decreased the levels of fasting blood glucose,ALT,AST,ALB,CRP,TNF-α and IL-6,reduced the liver index,down-regulated the mRNA expression of TNF-α in the liver,and ameliorated the pathologic changes of the liver.CONCLUSION: Sequoyitol attenuates liver lesions in type 2 diabetic rats through down-regulation of TNF-α and IL-6 expression.
引文
[1]Shakil A,Church RJ,Rao SS.Gastrointestinal complica-tions of diabetes[J].Am Fam Physician,2008,77(12):1697-1702.
[2]王音音,李桂峰,王霆.红杉醇在植物种类中的分布[J].今日药学,2008,18(1):70-74.
[3]孙明杰,王霆.用于糖尿病预防和治疗的红杉醇和红杉醇植物提取物:中国,CN1706369[P].2004.
[4]梁敬钰,吴斐华,鲍官虎,等.一种防治糖尿病的植物提取物及其制备方法与药物用途:中国,CN1488344A[P].2004.
[5]韩冰,谢汝佳,洪琴,等.miR-200s在中药丹芍化纤干预大鼠肝纤维化过程中的表达变化[J].中国病理生理杂志,2012,28(11):1950-1954.
[6]Harrison SA.Liver disease in patients with diabetes melli-tus[J].J Clin Gastroenterol,2006,40(1):68-76.
[7]Younossi ZM,Gramlich T,Liu YC,et al.Nonalcoholicfatty liver disease:assessment of variability in pathologicinterpretations[J].Mod Pathol,1998,11(6):560-565.
[8]Gawrieh S,Knoedler DM,Saeian K,et al.Effects of in-terventions on intra-and inter observer agreement on inter-pretation of nonalcoholic fatty liver disease histology[J].Ann Diagn Pathol,2011,15(1):19-24.
[9]Hossain N,Afendy A,Stepanova M,et al.Independentpredictors of fibrosis in patients with nonalcoholic fatty liv-er disease[J].Clin Gastroenterol Hepatol,2009,7(11):1224-1229.
[10]Czaja MJ,Liu H,Wang Y.Oxidant-induced hepatocyteinjury from menadione is regulated by ERK and AP-1 sig-naling[J].Hepatology,2003,37(6):1405-1413.
[11]Poli G.Pathogenesis of liver fibrosis:role of oxidativestress[J].Mol Aspects Med,2000,21(3):49-98.
[12]Czaja MJ.Cell signaling in oxidative stress-induced liverinjury[J].Semin Liver Dis,2007,27(4):378-389.
[13]Mirza S,Hossain M,Mathews C,et al.Type 2-diabetesis associated with elevated levels of TNF-α,IL-6 and adi-ponectin and low levels of leptin in a population of MexicanAmericans:a cross-sectional study[J].Cytokine,2012,57(1):136-142.
[14]Jiao K,Liu H,Chen J,et al.Roles of plasma interleu-kin-6 and tumor necrosis factor-αand FFA and TG in thedevelopment of insulin resistance induced by high-fat diet[J].Cytokine,2008,42(2):161-169.
[15]申锷,陈瑞珍,杨英珍,等.Apocynin降低1型糖尿病小鼠心肌组织炎症因子的表达[J].中国病理生理杂志,2009,25(11):2109-2112.
[2]王音音,李桂峰,王霆.红杉醇在植物种类中的分布[J].今日药学,2008,18(1):70-74.
[3]孙明杰,王霆.用于糖尿病预防和治疗的红杉醇和红杉醇植物提取物:中国,CN1706369[P].2004.
[4]梁敬钰,吴斐华,鲍官虎,等.一种防治糖尿病的植物提取物及其制备方法与药物用途:中国,CN1488344A[P].2004.
[5]韩冰,谢汝佳,洪琴,等.miR-200s在中药丹芍化纤干预大鼠肝纤维化过程中的表达变化[J].中国病理生理杂志,2012,28(11):1950-1954.
[6]Harrison SA.Liver disease in patients with diabetes melli-tus[J].J Clin Gastroenterol,2006,40(1):68-76.
[7]Younossi ZM,Gramlich T,Liu YC,et al.Nonalcoholicfatty liver disease:assessment of variability in pathologicinterpretations[J].Mod Pathol,1998,11(6):560-565.
[8]Gawrieh S,Knoedler DM,Saeian K,et al.Effects of in-terventions on intra-and inter observer agreement on inter-pretation of nonalcoholic fatty liver disease histology[J].Ann Diagn Pathol,2011,15(1):19-24.
[9]Hossain N,Afendy A,Stepanova M,et al.Independentpredictors of fibrosis in patients with nonalcoholic fatty liv-er disease[J].Clin Gastroenterol Hepatol,2009,7(11):1224-1229.
[10]Czaja MJ,Liu H,Wang Y.Oxidant-induced hepatocyteinjury from menadione is regulated by ERK and AP-1 sig-naling[J].Hepatology,2003,37(6):1405-1413.
[11]Poli G.Pathogenesis of liver fibrosis:role of oxidativestress[J].Mol Aspects Med,2000,21(3):49-98.
[12]Czaja MJ.Cell signaling in oxidative stress-induced liverinjury[J].Semin Liver Dis,2007,27(4):378-389.
[13]Mirza S,Hossain M,Mathews C,et al.Type 2-diabetesis associated with elevated levels of TNF-α,IL-6 and adi-ponectin and low levels of leptin in a population of MexicanAmericans:a cross-sectional study[J].Cytokine,2012,57(1):136-142.
[14]Jiao K,Liu H,Chen J,et al.Roles of plasma interleu-kin-6 and tumor necrosis factor-αand FFA and TG in thedevelopment of insulin resistance induced by high-fat diet[J].Cytokine,2008,42(2):161-169.
[15]申锷,陈瑞珍,杨英珍,等.Apocynin降低1型糖尿病小鼠心肌组织炎症因子的表达[J].中国病理生理杂志,2009,25(11):2109-2112.