PDF下载 ( 1612 KB)
Immunohistochemical expression of NF-κB, α-SMA and TGFβ1 in experimental hepatic injury rats
-
摘要: 目的探讨肝组织核转录因子-κB（NF-κB）、α-平滑肌动蛋白（α-SMA）、转化生长因子（TGF）β1在实验性肝损伤大鼠不同时期的免疫组化表达及其定位情况,探讨其在肝损伤过程中的变化规律及相互关系。方法采用四氯化碳（CCl4）复合因素诱发大鼠肝纤维化模型。50只SPF级SD大鼠随机分为2组:对照组20只、造模组（CCl4诱导）30只。造模组首次皮下注射40%CCl4橄榄油溶液2 ml/kg,以后每周2次背部皮下注射40%CCl4橄榄油溶液1.5 ml/kg,30%乙醇6 ml/kg隔日灌胃并给予高脂饮食连续造模10周;对照组首次皮下注射橄榄油2 ml/kg,以后每周2次皮下注射橄榄油1.5 ml/kg,正常饮水饮食连续10周。分别于实验第2、6、10周处死大鼠,进行HE染色及VG染色病理检查,采用免疫组化、计算机图像分析等技术,动态观察NF-κB、α-SMA及TGFβ1在对照组及肝损伤造模组不同时期的表达和定位特点,各组间进行统计学分析。结果肝损伤造模组NF-κB、α-SMA及TGFβ1表达均明显高于正常对照组（P<0.01）,在实验性肝损伤不同发展阶段,三种蛋白的表达逐渐增高...Abstract: Objective To study the immunolocation and expression of nuclear factor kappa B (NF-κB) 、alpha-SMA (α-SMA) and transforming growth factor-beta1 (TGFβ1) in different stages of experimental rats hepatic injury and discuss the possible effects and correlation in the development of liver injury.Methods Hepatic injury model rats were induced by multiple factors including carbon tertrachloride (CCl4) .Altogether 50 SD rats of SPF grade were randomly divided into two groups: normal control group (20rats) and model control group (30rats) .The model group rats were injected subcutaneously with 40% CCl4 olive oil (2 ml/kg) for the first time, and later the model rats were injected with CCl4 olive oil (40%, 1.5 ml/kg) twice a week for 6 weeks and 10 weeks, and in the meantime they were given orally with 30% ethanol (6 ml/kg) every other day and given a high-fat diet continuously for 6 weeks and 10 weeks;The normal group were injected subcutaneously with olive oil 2 ml/kg for the first time and later injected with olive oil (1.5 ml/kg) twice a week with normal water diet for 6 weeks and 10 weeks.Respectively the rats were killed after 6 weeks or 10 weeks and studied for general condition.In all the tested rats, their liver tissues were obtained for pathological observation and immunohistochemistry staining.The expression degree of NF-κB、α-SMA and TGFβ1 and changes of morphology in liver were measured by image analysis system.Results Hepatic injury models were successfully constructed.The expression of NF-κB、α-SMA and TGFβ1 were gradually increased in the different processes of experimental hepatic injury rats, respectively (P<0.01 or P <0.05) .There were distinctly positive correlation among the expression of NF-κB、α-SMA and TGFβ1 (r1=0.961, P1<0.01;r2=0.923, P2<0.01;r3=0.953, P3<0.01) .Conclusion NF-κB、α-SMA and TGFβ1 play significant role in the development of hepatic fibrosis and they play a reciprocal promoting role to lead the hepatic fibrosis.They can be regarded as one of the principal makers to predict the severe degree of hepatic fibrosis, meanwhile our results may provide theory foundation for us to target hepatic fibrosis through NF-κB、α-SMA and TGFβ1.
-
Key words:
- liver cirrhosis /
- experimental /
- NF-κB /
- actins
-
[1]Le Bousse-Kerdilès M, Marié-Claire M, Samson M.Cel-lular and molecular mechanisms underlying bone marrow andliver fibrosis:a review[J].Eur cytokine netw, 2008, 19 (2) :69-80. [2] Wynn TA.Cellular and molecular mechanisms of fibrosis[J]. J pathology, 2008, 214 (2) : 199-210. [3] Elsharkawy AM, Oakley F, Mann DA. The role and regulation of hepatic stellate cell apoptosis in reversal of liver fibrosis[J]. Apoptosis, 2005, 10 (5) : 927-939. [4]Li K.Mechanism of curcumine on the suppression of the ex-pression of TGF beta 1 and CTGF signaling pathway on ex-perimental hepatic fibrosis[J].Int J Infect Dis, 2010, 14:39-39. [5] OoYH, Shetty S, Adams DH. The Role of chemokines in the recruitment of lymphocytes to the liver[J]. Dig Dis, 2010, 34 (1) : 45-54. [6]Braz MM, Ramalho FS, Cardoso RL, et al.Slight activationof nuclear factor kappa-B is associated with increased he-patic stellate cell apoptosis in human schistosomal fibrosis[J].Acta Trop, 2010, 113 (1) :66-71. [7]Guicciardi ME, Gores GJ.Apoptosis as a Mechanism for Liv-er Disease Progression[J].Semin Liver Dis, 2010, 30 (4) :402-410. [8]Qin L, Han Y.Epigenetic Repression of Matrix Metalloprotei-nases in Myofibroblastic Hepatic Stellate Cells through His-tone Deacetylases 4 Implication in Tissue Fibrosis[J].Am JPathol, 2010, 177 (4) :1915-1928. [9]Czaja MJ.The future of GI and liver research:editorial per-spectives.Ⅲ.JNK/AP-1 regulation of hepatocyte death[J].Am J Physiol Gastrointest Liver Physiol, 2003, 284 (6) :G875-879. -
本文二维码
计量
- 文章访问数: 4646
- HTML全文浏览量: 18
- PDF下载量: 843
- 被引次数: 0
下载:
