Analysis of the Pathogenic Mechanism in Schistosomiasis-Functional Decline of the Mitochondria in Parenchymal Liver Cells

血吸虫病发病机制分析——肝细胞实质线粒体功能下降

• 批准号: 01570221
• 负责人: TANABE Masanobu
• 金额: $ 1.09万
• 依托单位: Department of Parasitoloby, School of Medicine, Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01570221/
• 关键词: Schistosoma mansoni; Hepatocyte; Mitochondria; Respiration; Mg<D1++@>D1-ATPase; Egg-granuloma; Free proline; 電子伝達系; NADH脱水素酵素

A mitochondria-rich fracion isolated from the livers of ICR and C3H female mice 8 to 10 weeks after Schistosoma mansoni infection showed to be uncoupling state of the succcinateーsupported respiration. A moderate to strong mitochondrial Mg^<++>-dependent ATPase activity at neutral pH was demonstrated cytochmecally in the parenchymal liver cells of S. mansoni-infected mice. Moreover, the enzymatic activities of malate dehydrogenase, NADH dehydrogenase, cytochrome oxidase and glutamate dehydrogenase also decreased significantly in the mitochondria-rich fraction from the livers of infected mice. Furthermore, an ultrastructural observation of the liver of infected mice clearly demonstrated some morphological changes of hepatic mitochondria, i. e., swelling, disappearance of cristae and deciline of electron density of matrix.The uncoupling state of the respiration and the ultrastructural changes of the hepatic mitochondria were also demonstrated in the uninfected, normal mice treated with in … More traperitoneal injection of the dialysate of 15,000g x 30 min supernatant of crude extracts of egg-granulomas. However, there was no appreciable change in the respiration of hepatic mitochondria in the mice treated with culture fluid or crude extract of S. mansoni adult worms. The active substance was partially purified from crude extract of egg-granulomas by ammonium sulfate fractionation, Sephadex G-200 gel filtration and DEAEーsephadex A-25 column chromatography. Intraperitoneal injection of the partially purified substance into unifected, normal mice resulted in the decline of the activities of several enzymes in hepatic metochondria and in the ultrastructural changes in the mitochondria of parencymal liver cells. The same biochemical changes were also observed in the primary cultured hepatocytes treated with the partially purified substance.These findings suggest that the egg-granulomas produce some substance(s) which may be responsible for reduction of the activities of respiration and several enzymes localized in the mitochondria of the parenchymal liver cells in S. mansoni-infected mice. Less

从感染曼氏血吸虫8 ~ 10周的ICR和C_3H雌性小鼠肝脏中分离到一个富含琥珀酸的组分，表明该组分是琥珀酸盐支持呼吸的解偶联状态。在中性pH条件下，S.感染曼氏菌的小鼠。此外，苹果酸脱氢酶，NADH脱氢酶，细胞色素氧化酶和谷氨酸脱氢酶的酶活性也显着下降，从感染小鼠的肝脏富含维生素A的部分。此外，对感染小鼠肝脏的超微结构观察清楚地表明了肝脏线粒体的一些形态学变化，即：例如，结果表明，感染组小鼠肝细胞线粒体的超微结构发生了改变，线粒体的呼吸呈解偶联状态，线粒体的呼吸呈解偶联状态 ...更多信息 腹膜内注射15，000 g × 30 min虫卵肉芽肿粗提物上清液透析液。但用S.曼氏蠕虫经硫酸铵分级沉淀、SephadexG-200凝胶过滤和DEAE-SephadexA-25柱层析，从虫卵肉芽肿粗提物中部分纯化出活性物质。将部分纯化的物质腹腔注射到未感染的正常小鼠中，导致肝代谢酶中几种酶的活性下降和肝实质细胞线粒体的超微结构变化。用部分纯化的物质处理原代培养的肝细胞，也观察到同样的生化变化，这些结果表明，虫卵肉芽肿产生的某些物质可能与S.感染曼氏菌的小鼠。少

项目成果

田邊 將信: "住血吸虫症における肝線維化機構の現状" 慶應医学. 66. 945-952 (1989)

Masanobu Tanabe：“血吸虫病肝纤维化机制的现状”Keio Igaku 66. 945-952 (1989)

Masanobu Tanabe et al.: "Elevation of laminin and beta-subunit of prolyl 4-hydroxylase in the sera of human subjects with schistosomiasis mansoni" Japanese Journal of Experimental Medicine. 59. 109-119 (1989)

Masanobu Tanabe 等人：“曼氏血吸虫病患者血清中层粘连蛋白和脯氨酰 4-羟化酶 β 亚基的升高”《日本实验医学杂志》。

Tanabe, M., Kaneko, N. & Takauchi, T: "_<Schistosoma> _<mansoni>:Suppression of carbamoyl phosphate synthetase (ammonia) and ornithine carbamoyltransferase acitivities in the liver of infected mice." Experimental Parasitology. 68. 432-442 (1989)

田边，M.，金子，N.

Miyahira,Y.,Takeuchi,T.,Okuzawa,E.,Motta,S.,Tanabe,M.,Miura,S.et al: "Pathogenic Entamoeba histolytica infection in a steady couple of Japanese homosexual men." Japanese Journal of parasitology. 39. 497-499 (1990)

Miyahira,Y.、Takeuchi,T.、Okuzawa,E.、Motta,S.、Tanabe,M.、Miura,S.等人：“一对日本同性恋男性中的致病性溶组织内阿米巴感染。”

Masanobu Tanabe et al.: "Schistosoma mansoni:Suppression of carbamoyl phosphate synthetase(ammonia)and ornithine carbamoyltransferase activities in the liver of infected mice" Experimental Parasitology. 68. 432-442 (1989)

Masanobu Tanabe 等人：“曼氏血吸虫：受感染小鼠肝脏中氨基甲酰磷酸合成酶（氨）和鸟氨酸氨基甲酰转移酶活性的抑制”实验寄生虫学。