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[从五味子果实中分离出的木脂素化合物TJN-101对四氯化碳诱导的慢性肝损伤大鼠肝纤维化及部分肝切除术后肝脏再生的影响]

[Effects of TJN-101, a lignan compound isolated from Schisandra fruits, on liver fibrosis and on liver regeneration after partial hepatectomy in rats with chronic liver injury induced by CCl4].

作者信息

Takeda S, Kase Y, Arai I, Ohkura Y, Hasegawa M, Sekiguchi Y, Tatsugi A, Funo S, Aburada M, Hosoya E

机构信息

Tsumura Research Institute for Pharmacology, Ibaraki, Japan.

出版信息

Nihon Yakurigaku Zasshi. 1987 Jul;90(1):51-65. doi: 10.1254/fpj.90.51.

Abstract

TJN-101 ((+)-(6S,7S,R-biar)-5,6,7,8-tetrahydro-1,2,3,12-tetramethoxy -6,7-dimethyl-10,11-methylenedioxy-6-dibenzo[a,c]cyclooctenol) is one of the lignan compounds isolated from Schisandra fruits. 1) Effect of TJN-101 on liver fibrosis was investigated in rats which were injected with CCl4 (1 ml/kg) subcutaneously twice a week for 12 weeks. TJN-101 was given orally at the dose of 10 or 30 mg/kg/day for 6 or 3 weeks beginning on the 6th or 9th week after the start of CCl4-intoxication, respectively. The elevations of serum transaminase activities and the increase of liver 4-hydroxyproline content were observed depending on the period of CCl4-intoxication. These changes were marked on the 9th and 12th weeks after. In the histopathological study, the degenerative fatty change on the 6th week after and the formation of pseudolobule caused by fibrosis proliferation on the 9th or 12th week after were mainly observed. When rats were treated with TJN-101, the abnormalities in biochemical parameters and the fibrosis proliferation caused by CCl4-intoxication were improved. 2) Chronic liver injury was induced by the treatment with CCl4 (1 ml/kg) subcutaneously twice a week for 10 weeks to investigate the effect of TJN-101 on liver regeneration after partial hepatectomy. TJN-101, which was given orally at the dose of 10, 30 or 100 mg/kg/day for 6 days from the 1st day after partial hepatectomy, dose-dependently increased the liver regeneration rate and improved the serum BSP retention rate. These results suggest that TJN-101 suppresses the fibrosis proliferation and accelerates both the liver regeneration and the recovery of liver function after partial hepatectomy in chronic liver injury.

摘要

TJN-101((+)-(6S,7S,R-biar)-5,6,7,8-四氢-1,2,3,12-四甲氧基-6,7-二甲基-10,11-亚甲基二氧基-6-二苯并[a,c]环辛烯醇)是从五味子果实中分离出的木脂素类化合物之一。1)在每周两次皮下注射四氯化碳(1毫升/千克),持续12周的大鼠中研究TJN-101对肝纤维化的影响。分别在四氯化碳中毒开始后的第6周或第9周开始,以10或30毫克/千克/天的剂量口服TJN-101,持续6周或3周。根据四氯化碳中毒的时间,观察到血清转氨酶活性升高以及肝脏4-羟脯氨酸含量增加。这些变化在第9周和第12周后较为明显。在组织病理学研究中,主要观察到第6周后的退行性脂肪变性以及第9周或第12周后由纤维化增殖引起的假小叶形成。当用TJN-101治疗大鼠时,四氯化碳中毒引起的生化参数异常和纤维化增殖得到改善。2)通过每周两次皮下注射四氯化碳(1毫升/千克),持续10周来诱导慢性肝损伤,以研究TJN-101对部分肝切除术后肝再生的影响。从部分肝切除术后第1天开始,以10、30或100毫克/千克/天的剂量口服TJN-101,持续6天,剂量依赖性地提高了肝再生率并改善了血清BSP潴留率。这些结果表明,TJN-101在慢性肝损伤中可抑制纤维化增殖,并加速部分肝切除术后的肝再生和肝功能恢复。

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