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1-[(2-噻唑啉-2-基)氨基]乙酰基-4-(1,3-二硫杂环戊烯-2-亚基)-2,3,4,5-四氢-1H-1-苯并氮杂卓-3,5-二酮盐酸盐(KF-14363)对部分肝切除大鼠肝脏再生及肝线粒体功能的影响

Effects of 1-[(2-thiazolin-2-yl)amino]acetyl-4-(1,3-dithiol 2-ylidene)-2,3,4,5-tetrahydro-1H-1-benzazepin-3,5-dione hydrochloride (KF-14363) on liver regeneration and function of hepatic mitochondria in partially hepatectomized rats.

作者信息

Yoshitake I, Ohishi E, Kubo K

机构信息

Pharmaceutical Research Laboratories of Kyowa Hakko Kogyo Co., Shizuoka, Japan.

出版信息

J Pharmacobiodyn. 1992 Jan;15(1):39-47. doi: 10.1248/bpb1978.15.39.

Abstract

Effects of 1-[(2-Thiazolin-2-yl)amino]acetyl-4-(1,3-dithiol 2-ylidene)-2,3,4,5-tetrahydro-1H-1-benzazepin-3,5-dione hydrochloride (KF-14363), a hepatoprotective compound, on liver regeneration, liver nucleic acid levels, mitochondrial respiration activity and hepatic energy metabolism after partial hepatectomy (OPE) in rats were studied. The liver regeneration rate was significantly increased in rats administered 100 mg/kg of KF-14363 for 6 d as compared with the control group administered vehicle. The serum glucose level in rats administered 100 mg/kg of KF-14363 measured 3 h after OPE (OPE 3 h) was significantly higher than that in rats administered vehicle (group A) and the serum insulin level in the KF-14363 group was more than double that of group A. KF-14363 also significantly increased liver nucleic acid levels in OPE rats. In mitochondrial function experiments, KF-14363 (100 mg/kg) was orally administered 2 h after OPE. Three hours after OPE (1 h after KF-14363 administration), state 3 respiration was significantly higher in the OPE 3 h + KF-14363 group than in the OPE 3 h + water group. The adenosine diphosphate/oxygen (ADP/O) ratio was also significantly higher in the OPE 22 h (22 h after OPE) + KF-14363 group than in the OPE 22 h + water group. On hepatic energy metabolism, KF-14363 increased adenosine diphosphate and triphosphate levels. Total adenine nucleotide level in the OPE 3 h + KF-14363 group was significantly higher than that in the OPE 3 h + water group. Adenylate energy charge (AEC) was slightly decreased in the OPE 3 h + water group and significantly decreased in the OPE 22 h + water group than in the corresponding sham group.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

研究了具有肝脏保护作用的化合物1-[(2-噻唑啉-2-基)氨基]乙酰基-4-(1,3-二硫醇-2-亚基)-2,3,4,5-四氢-1H-1-苯并氮杂卓-3,5-二酮盐酸盐(KF-14363)对大鼠部分肝切除(OPE)后肝脏再生、肝脏核酸水平、线粒体呼吸活性及肝脏能量代谢的影响。与给予赋形剂的对照组相比,给予100mg/kg KF-14363共6天的大鼠肝脏再生率显著提高。OPE后3小时(OPE 3h)测量,给予100mg/kg KF-14363的大鼠血清葡萄糖水平显著高于给予赋形剂的大鼠(A组),且KF-14363组的血清胰岛素水平是A组的两倍多。KF-14363还显著提高了OPE大鼠的肝脏核酸水平。在线粒体功能实验中,OPE后2小时口服给予KF-14363(100mg/kg)。OPE后3小时(KF-14363给药后1小时),OPE 3h + KF-14363组的状态3呼吸显著高于OPE 3h + 水组。OPE 22小时(OPE后22小时)+ KF-14363组的二磷酸腺苷/氧(ADP/O)比值也显著高于OPE 22小时 + 水组。在肝脏能量代谢方面,KF-14363提高了二磷酸腺苷和三磷酸水平。OPE 3h + KF-14363组的总腺嘌呤核苷酸水平显著高于OPE 3h + 水组。腺苷酸能量电荷(AEC)在OPE 3h + 水组略有下降,在OPE 22小时 + 水组比相应的假手术组显著下降。(摘要截短于250字)

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