摘要
目的探讨TNF-α,IL-6及IL-10在实验性大鼠肝纤维化进程中的作用。方法清洁级SD大鼠100只,随机分为3组。正常对照组(C组)24只,腹腔内注射生理盐水2mL·kg^(-1),2次·wk^(-1);模型组(M组)40只及治疗组(T组)36只,腹腔内注射500mL·kg^(-1)CCl_4,2mL·kg^(-1),2次·wk^(-1);E组从3wk起,注射CCl_4前腹腔内注射IL-10 4ug·kg^(-1).于5wk,7wk,9wk分别随机选取C组动物7只,M,E组动物各10只颈动脉插管取血,留取肝脏,ELISA法测定血清中TNF-α,IL-6及IL-10水平,肝脏常规石蜡切片,银染。结果肝脏病理组织学检查证实成功构建CCl_4诱导的实验性大鼠肝纤维模型,且随注射CCl_4次数增多,肝纤维化程度逐渐加重,同时期动物T组较M组肝纤维化程度减轻.C组血清TNF-α、IL-6及IL-10水平分别为(15.2±3.8)ng·L^(-1),(63.6±33.0)ng·L^(-1)和(132.9±22.1)ng·L^(-1);M组水平分别为(18.9±5.3)ng·L^(-1),(89.1±25.4)ng·L^(-1)和(57.6±18.9)ng·L^(-1);T组水平分别为(14.0±1.9)ng·L^(-1),(74.7±21.2)ng·L^(-1)及(88.2±20.8)ng·L^(-1).wk5,7,9,M组TNF-α动态变化水平分别为(16.5±2.7)ng·L^(-1),(17.1±0.9)ng,L^(-1),(22.6±6.8)ng·L^(-1);T组水平分别为(13.4±1.0)ng·L^(-1),(13.6±1.2)ng·L^(-1),(14.5± 2.9)ng·L^(-1);M组IL-6动态变化水平分别为(63.8±12.2)ng·L^(-1),(71.5±16.1)ng·L^(-1),(112.3±20.2)ng·L^(-1),T组水平分别为(63.1±13.1)ng·L^(-1),(70.1±11.8)ng·L^(-1),(85.8±11.6)ng·L^(-1);M组IL-10动态变化水平分别为(82.1±5.2)ng·L^(-1),(65.7±8.4)ng·L^(-1),(50.0±8.5)ng·L^(-1),M组TNF-α及IL-6水平显著高于C组和T组(P<0.05),且在肝纤维化进程中呈动态上升趋势,经IL-10干预后,二者水平下降与M组有明显差异(P<0.05).M组IL-10水平低于N组(P<0.05),在肝纤维化进程中呈动态下降趋势。结论 TNF-α,IL-6升高及IL-10降低在肝纤维化进程中起重要促进作用,予以外源性IL-10对CCl_4诱导的肝纤维化有明显拮抗作用。
AIM To investigate the role of tumor necrosis factor α, interleukin-6 and interleukin-10 on experimental rat liver fibrosis. METHODS One hundred clean SD rats were divided randomly into 3 groups: control group (intraperitoneal injection of saline 2mL·kg^(-1), 2·wk^(-1)), model group (intraperitoneal injection of 500mL·L^(-1) CCI_4 2mL·kg^(-1), 2· wk^1), IL-10 group (in addition to the same dosage of CCI_4, intraperitoneal injection of IL-10 4μg·kg^(-1) was mede from week 3). In week 5, 7 and 9, the rats of the three groups were selected randomly to collect plasma and resect liver. The serum levels of TNF-α, IL-6 and IL-10 were measured by enzyme linked immunosorbent assay (ELISA), liver tissues were made into paraffin section with sliver staining. RESULTS The CCI_4-induced experimental rat hepatic fibrosis model was successfully established and liver fibrosis was developed with the injection of CCI_4. The TNF-α, IL-6 and IL-10 levels in serum of group C were 15.2 ±3.8ng·L^(-1), 63.6±33.0ng·L^(-1) and 132.9±22.1ng·L^(-1) respectively; group M were 18.9±5.3ng·L^(-1), 89.1±25. 4ng·L^(-1) and 57.6±18.9ng·L^(-1) respectively; group T were 14.0±1.9ng·L^(-1), 74.7±21.2ng·L^(-1) and 88.2±20.8ng·L^(-1). The TNF-αlevels in group M at week 5,7, 9 were 16.5± 2.7ng·L^(-1), 17.1±0.9ng·L^(-1), 22.6±6.8ng·L^(-1) and 13.4±1. 0ng·L^(-1), 13.6±1.2ng·L^(-1), 14.5±2.9g·L^(-1) in group T respectively; the IL-6 levels in group M at three stage were 63.8±12.2ng·L^(-1), 71.5±16. 1ng·L^(-1), 112.3±20.2ng· L^(-1) and 63.1±13.1ng·L^(-1), 70.1±11.8ng·L^(-1), 85.8±11.6ng ·L^(-1) in group Trespectively; the IL-10 levels in group Min the three stage were 82.1±5.2ng·L^(-1), 65.7±8.4ng·L^(-1) and 50.0±8.5ng·L^(-1). The levels of TNF-α and IL-6 in group M were significantly higher then that in group C and group T (P<0.05) and tended to increase in the progress of hepatic fibrosis, however, the levels of TNF-α and IL-6 in group T after treated by IL-10 were significantly lower than that in group M(P<0.05). The level of IL-10 in group M was significantly lower than that in group C(P<0.05). CONCLUSIONS TNF-α, IL-6 and IL-10 play important roles in the progress of hepatic fibrosis, IL-1O has fibrogenesis- inhibiting effect on the CCI_4-induced rat hepatic fibrosis.
出处
《世界华人消化杂志》
CAS
2001年第11期1242-1245,共4页
World Chinese Journal of Digestology
基金
福建省教委基金.No.JA01070
关键词
肝硬化
病理生理学
肿瘤坏死因子
白介素6
白介素10
Liver cirrhosis
experimental /physiopathology
tumor necmeis factor
Interleukin-6
interleukin-10
