Effects of CH-100, a Chinese herbal medicine, on acute concanavalin A-mediated hepatitis in control and alcohol-fed rats

Effects of CH-100, a Chinese herbal medicine, on acute concanavalin A-mediated hepatitis in control and alcohol-fed rats
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DOI:
10.1097/00000374-200006000-00015
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发表时间:
2000-06-01
影响因子:
3.2
通讯作者:
Cao, Q
Cao, Q
中科院分区:
医学3区
文献类型:
--
作者:
Batey, R;Cao, Q

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背景资料:伴刀豆球蛋白A(Con A)的管理导致急性肝炎,涉及T细胞活化和炎症介质的生产在小鼠和大鼠。我们研究的作用CH-100,一种中草药以前在人类丙型肝炎试验,在预防Con A相关的,T细胞介导的,急性肝损伤rates.Methods:雌性Wistar大鼠喂养40%乙醇,2%蔗糖,或isocaloric蔗糖8周。同时,这些动物每天在饲料中喂食中草药CH-100(4片/kg体重/天)或安慰剂。在摄入乙醇0、4和8周时,从尾静脉采集血液用于内毒素(脂多糖)测定。注射Con A(20 mg/kg体重)或磷酸盐缓冲盐水后24小时,从尾静脉采集血液用于丙氨酸氨基转移酶和肿瘤坏死因子(TNF)-α测定。从肝灌注液中分离肝相关C4(+)T细胞,然后与Con A(5 μ g/ml)在37 ℃下培养24小时。检测血液和肝脏灌流液中CD 4(+)T细胞的比例。收集肝脏样品进行组织病理学分析。结果:与安慰剂治疗的大鼠相比,CH-100治疗的乙醇喂养大鼠的Lipopopaccharide水平显着降低。Con A注射后,与安慰剂治疗的大鼠相比,草药治疗的大鼠在12和24小时的丙氨酸氨基转移酶水平较低。此外,血清TNF-α水平较低的乙醇喂养的大鼠中草药治疗。在CH-100处理的乙醇喂养大鼠中,观察到培养的肝脏相关CD 4(+)T细胞的TNF-α产生显著减少。CH-100治疗与所有组中血液和肝脏灌注液中CD 4(+)细胞百分比的降低相关。与安慰剂喂养的大鼠相比,草药治疗的大鼠显示出明显较少的肝坏死和减少的CD 4(+)T细胞在门脉区域的浸润。结论:结果表明,CH-100修改了T细胞对Con A注射的反应。这种作用在乙醇喂养的大鼠中更为显著,这表明CH-100在治疗酒精性肝病中可能发挥作用。
Background: Administration of concanavalin A (Con A) leads to acute hepatitis that involves T-cell activation and inflammatory mediator production in mice and rats. We examined the role of CH-100, a Chinese herbal medicine previously trialed in human hepatitis C, in the prevention of Con A-related, T-cell-mediated, acute liver injury in rats.Methods: Female Wistar rats were fed 40% ethanol, 2% sucrose, or isocaloric sucrose for 8 weeks. At the same time, these animals were fed either the Chinese herbal medicine CH-100 (4 tablets/kg body weight/ day) or placebo in chow daily. Blood from the tail vein was collected for endotoxin (lipopolysaccharide) assay at 0, 4, and 8 weeks of ethanol consumption. Twenty-four hours after injection of Con A (20 mg/kg body weight) or phosphate-buffered saline, blood from the tail vein was collected for alanine aminotransferase and tumor necrasis factor (TNF)-alpha assays. Liver-associated C4(+) T cells were isolated from liver perfusates and then cultured with Con A (5 mu g/ml) at 37 degrees C for 24 hr. Supernatants were harvested for TNF-alpha assay. The proportion of CD4(+) T cells in blood and liver perfusates was measured. Liver samples were collected for histopathological analysis.Results: Lipopolpaccharide levels were significantly reduced in CH-100-treated ethanol fed rats compared with placebo-treated rats. After Con A injection, alanine aminotransferase levels were lower at 12 and 24 hr in herb-treated rats compared with placebo-treated rats. Furthermore, serum TNF-a levels were lower in ethanol-fed rats on herbal treatment. A significant decrease in TNF-alpha production by liver-associated CD4(+) T cells in culture was observed in CH-100-treated ethanol-fed rats. CH-100 treatment was associated with a decreased percentage of CD4(+) cells in both blood and liver perfusate in all groups. Herb-treated rats displayed markedly less hepatic necrosis and a reduced CD4(+) T-cell infiltrate in portal areas than did placebo-fed rats.Conclusions: The results demonstrate that CH-100 modified the T-cell response to Con A injection. The effect was more marked in ethanol-fed rats, which suggests a possible role for CH-100 in treating alcoholic liver disease.