Gadolinium chloride inhibits the spontaneous resolution of fibrosis in CCL4-induced cirrhosis
Gadolinium chloride inhibits the spontaneous resolution of fibrosis in CCL4-induced cirrhosis
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DOI：
10.1080/15376510600773446
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发表时间：
2006-11-01
影响因子：
3.2
通讯作者：
Muriel, Pablo
中科院分区：
文献类型：
--
作者：
Chavez, Enrique;Alcantar, Lidia K.;Muriel, Pablo
目前的证据表明，肝纤维化是动态的，可以是双向的，涉及进展期和退化期，除了增加基质合成外，这一病理过程还涉及基质降解调节的重大变化。也有证据表明，Kupffer细胞参与了纤维形成和纤维溶解。因此，本研究的目的是研究枯否细胞在肝纤维化自发消退中的作用。雄性Wistar大鼠慢性CCl4染毒3个月后，停用CCl4，分成2组：1组给予Gd(10 mg/kg，ip，每日1次)，另1组仅给予溶剂(水)2个月。血清碱性磷酸酶和丙氨酸氨基转移酶活性及肝脏脂质过氧化作用在CCl4处理后升高，但在停止CCl4处理后恢复正常。CCl4可显著降低GSH、GSH/GSSG和GSH+GSSG，但停用CCl4可使谷胱甘肽指标恢复正常。CCl4治疗使肝纤维化增加了5倍，糖原显著降低，而停用CCl4则完全逆转了糖原耗竭和部分纤维化。氯化Gd仅对糖原和胶原含量有影响，前者进一步降低，后者在停药后仍保持升高。Kupffer细胞的选择性抑制剂Gd Cl2诱导的持续性纤维化表明，这些细胞在纤维溶解中起着关键作用。
Current evidence indicates that liver fibrosis is dynamic and can be bidirectional, involving phases of progression and regression, and that in addition to increased matrix synthesis, this pathological process involves major changes in the regulation of matrix degradation. There is also evidence that Kupffer cells participate in both fibrogenesis and fibrolysis. Therefore, the aim of the present work was to study the participation of Kupffer cells on the spontaneous resolution of hepatic fibrosis. Cirrhosis was produced by 3 months of chronic CCl4 intoxication in male Wistar rats, and then CCl4 was discontinued and two groups were formed: One group received gadolinium chloride (10 mg/kg, IP, daily) and the other received the vehicle (water) only for 2 months. Serum enzyme activities of alkaline phosphatase and alanine aminotransferase and liver lipid peroxidation increased by CCl4 treatment but returned to normal by discontinuation of CCl4. GSH, GSH/GSSG, and GSH+GSSG decreased significantly by CCl4, but withdrawal of CCl4 restored normal glutathione parameters. Fibrosis increased five-fold and glycogen decreased significantly by CCl4 treatment, while discontinuation of CCl4 reversed completely glycogen depletion and partially fibrosis. Gadolinium chloride showed effects only in the content of glycogen and collagen; the former was decreased further and the latter remained elevated despite discontinuation of the toxic agent. Persistent fibrosis induced by gadolinium chloride, a selective inhibitor of Kupffer cells, indicates that these cells play a pivotal role in fibrolysis.