摘要
目的:探讨甘氨酸(Gly)对内毒素(LPS)性肝损害的保护机制．方法:BALB／c小鼠随机分为三组,LPS组(n= 50)经腹腔注射10 mg／kg的LPS,Gly组(n=50) 在注射相同剂量LPS前3 d开始喂饲含50 g／L 的Gly的饲料,正常生理盐水对照组(n=50), 经腹腔注射等体积的生理盐水,光镜观察组织病理学改变,免疫组织化学法检测TLR4表达水平:ELISA法检测血浆TNF-α,IL-10浓度及 RT-PCR检测肝组织中TNF-α,IL-10及TLR4的 mRNA表达水平．结果:Gly能明显提高小鼠存活率,肝脏病理损害程度减轻:Gly组TNF-α水平显著低于LPS 组,差异有统计学意义(708．83±51．29 ng／L vs 1852．8±126．64 ng／L,F=786．21,P<0．05);Gly 组IL-10N加且高峰前移,与LPS组比较差异有统计学意义(418．64±38．86 ng／L vs 211．15 ±26．44 ng／L,P<0．05);Gly组肝组织中TNF-α及TLR4表达也明显减弱,IL-10表达明显增强, 与LPS组比较差异均有统计学意义(分别为 TNF-α A值:1．59±0．14 vs 0．91±0．11;TLR4 A值:0．97±0．12 vs 0．53±0．11;IL-10A值:0．62 ±0．08 vs 1．06±0．15;P均<0．05)．结论:Gly能明显减轻LPS所致的肝损害,其机制可能与其下调肝细胞的TLR4表达,同时上调IL-10的水平有关．
AIM： To explore the protective mechanisms of glycine on liopolysaccharide （LPS）-induced liver injury.
METHODS： BABL/c mice were randomly divided into LPS group （n=50）, glycine group （n= 50）, and control group （n=50）. The animals in LPS and glycine groups were intraperitoneally injected with 10 mg/kg LPS to establish the liver injury model, while animals in glycine group were pretreated with 50 g/L glycine-containing food 3 d before modeling. The mice in control group received the same amount of normal saline. Liver samples were collected to observe histopathological changes. The levels of tumor necrosis factor-α （TNF-α） and interleukin-10（IL-10） in plasma were measured by enzyme linked immunosorbent assay （ELISA）. The mRNA expression of TNF-α, IL-10 and toll like receptor 4 （TLR4） in hepatic tissues were detected by reverse transcription-polymerase chain reaction （RT-PCR）. The expression of TLR4 protein inliver was detected with immunohistochemistry.
RESULTS： Glycine improved the survival rates of the mice, and attenuated LPS-induced pathological changes of the liver tissues significantly. The plasma level of TNF-α was markedly lower in glycine group than that in LPS group （708.83±51.29 ng/L vs 1852.8 ±126.64 ng/L, F786.21, P〈0.05） at 3 h, while the level of IL-10 was significantly higher at 12 h （418.64±38.86 ng/L vs 211.15± 26.44 ng/L, P〈0.05）. The expression of TNF-α and TLR4 were notably decreased in glycine group in comparison with those in LPS group （A value： 1.59±0.14 vs 0.91 ＋ 0.11, P 〈 0.05; 0.97±0.12 vs 0.53±0.11, P 〈 0.05）, but the expression of IL-10 was remarkably increased （A value： 0.62±0.08 vs 1.06±0.15, P〈0.05）.
CONCLUSION： Glycine pretreatment can attenuate LPS-induced liver injury, which may be associated with the down-regulation of TLR4 expression and up-regulation of IL-10 production.
出处
《世界华人消化杂志》
CAS
北大核心
2006年第16期1561-1565,共5页
World Chinese Journal of Digestology
基金
国家自然科学基金资助项目
No.30471696~~
关键词
甘氨酸
肝脏
内毒素
TOLL样受体4
Glycine
Liopolysaccharide
Toll like re-ceptor 4
Uver injury
