摘要
目的利用精密肝切片(PCLS)技术,研究吲哚-3-原醇(I3C)对乙醛活化肝星状细胞(HSCs)的作用及其机制。方法将200～800μmol.L-1的I3C及700μmol.L-1乙醛与PCLS共同孵育6h,免疫组化法分析肝切片中α-平滑肌肌动蛋白(α-SMA)表达,并检测培养液中谷胱甘肽S-转移酶(GST)和乳酸脱氢酶(LDH)活性、转化生长因子-β1(TGF-β1)含量、基质金属蛋白酶-1(MMP-1)及基质金属蛋白酶抑制物-1(TIMP-1)表达量及组织丙二醛(MDA)和羟脯氨酸(Hyp)含量。结果200～800μmol.L-1I3C可不同程度的减少乙醛激活的HSCs,并可明显降低乙醛升高的培养液中GST、LDH活性和肝组织中MDA和Hyp含量(P<0.05或P<0.01),呈良好的浓度依赖性。I3C给药组与乙醛对照组比较,培养液中TGF-β1含量降低(P<0.01),MMP-1/TIMP-1蛋白表达比值升高(P<0.01)。结论I3C能有效拮抗乙醛所致的HSCs活化,其机制与降低细胞氧化应激和促进基质胶原降解有关。
Aim To investigate effects of indole-3-car- binol （I3C） on hepatic stellate cells （HSCs） activated by acetaldehyde in precision-cut liver slices （PCLS）. Methods PCLS were incubated with 700μmol·L^-1 acetaldehyde and 200～ 800 μmol·L^-1 I3C for 6 h. The expression of α-smooth muscle actin （ot-SMA） in liver slices was analyzed by immunohistochemistry. The leakages of glutathione S-transferase （ GST）, lactate dehydrogenase （LDH） and content of transforming growth factor-β1 （TGF-β1） in media were assayed. Contents of malondialdehyde （MDA） and hydroxyproline （Hyp） in tissue were also determined. Expressions of matrix metalloproteinases-1 （ MMP-1 ） and tissue inhibitor of metalloproteinase （ TIMP-1 ） in media were analyzed by the western blot. Results The increase of activated HSCs due to acetaldehyde was inhibited by I3C （200～800μmol·L^-1）. Meanwhile, I3C treatment （200～ 800μmol·L^-1） showed significant and concentration-dependent antagonistic actions on the increment of GST, LDH leakages into the media and MDA, Hyp contents in tissues induced by acetaldehyde. The increase of TGF-β1 was also remarkable inversed by I3C （200～800μmol·L^-1 ）. As compared with acetaldehyde group, the ratio of MMP-1/ TIMP-1 was increased significantly by I3C treatment （800μmol·L^-1） （p〈0.01）. Conclusions 13C markedly protects liver slices from acetaldehyde-induced HSC activation, and it might involve the mechanism of the antioxidation against acetaldehyde and the promotion of ECM degradation.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2007年第4期441-445,共5页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No30371666)
关键词
吲哚-3-原醇
乙醛
精密肝切片技术
肝星状细胞
激活
indole-3-carbinol
acetaldehyde
precision-cut liver slices
hepatic stellate cells
activation
