白细胞介素-10对内毒素血症大鼠肝损伤的影响

Effects of interlukin-lO on lipopolysaccharide-induced liver injury in rats

目的评价白细胞介素-10（IL10）对内毒素血症大鼠肝损伤的影响。方法清洁级雄性Wislar大鼠100只，10～14周龄，体重250～300g，采用随机数字表法，将其随机分为5组（n=20）：对照组（C组）、内毒素血症组（LPS组）、IL-10组（1L-10组）、HO-1诱导剂钻原卟啉Ⅸ组（co组）和HO-1抑制剂锌原卟啉Ⅸ组（zn组）。LPS组、IL-10组、co组和zn组腹腔注射脂多糖（LPS）20mg／kg，IL-10组、co组和zn组于给予LPS前3h腹腔注射重组人IL-10.1μg，Co组和zn组分别于给予重组人IL-10后2h腹腔注射钴原卟啉Ⅸ和锌原卟啉Ⅸ25mg／kg。每组于注射LPS后24h时取10只大鼠，采集心脏全血，测定血清谷草转氨酶（ALT）、谷丙转氨酶〈AST）、肿瘤坏死因子-a（TNF．n）和白细胞介素-1B（IL1B）的水平；然后取肝组织，测定谷胱甘肽过氧化物酶（GSH-Px）和超氧化物歧化酶（SOD）活性、丙二醛（MDA）含量和血红素氧合酶。1（HO-1）mRNA表达。每组取10只大鼠，记录给予LPS后72h内大鼠生存情况。结果与c组比较，LPs组、IL10组、c0组和zn组血清ALT、AST、TNF—d、IL-18水平和肝组织MDA含量升高，肝组织GSH—Px、SOD活性和生存率降低（P〈0．05）；与LPS组比较，IL-10组和c0组血清ALT、AST、TNF-a IL-Iβ水平和肝组织MDA含量降低，肝组织GSH—Px、SOD活性、HO-1mRNA表达和生存率升高（P〈0．05）；与IL-10组比较，zn组血清ALT、AST、TNF-a、IL-1β水平和肝组织MDA含量升高，肝组织GSH．Px、SOD活性和生存率降低（P〈0．05），co组上述指标差异无统计学意义（P〉0．05）。结论IL-10可减轻内毒素血症大鼠肝损伤，其机制与诱导HO-1表达有关。

Objective To investigate the effects of interlukin-10 （IL-10） on lipopolysaccharide （LPS）-induced liver injury in rats. Methods One hundred male Wistar rats, aged 10-14 weeks, weighing 250-300 g, were randomly divided into 5 groups （ n = 20 each） ： control group （C group）, LPS group, IL-10 group, HO-1 inducer cobalt protoporphyrin-Ⅸ group （Co group） and HO-1 inhibitor zinc protoporphyrin-Ⅸ group （Zn group）. The animals in LPS, IL-10, Co and Zn groups received intraperitoneal LPS 20 mg/kg. IL-10, Co and Zn groups received recombinant human IL-10 1 μg at 3 h before LPS injection. Co and Zn groups received cobalt protoporphyrin-Ⅸ and zinc protoporphyrin-Ⅸ 25 mg/kg at 2 h before administration of recombinant human IL-10. Ten rats in each group were chosen at 24 h after LPS injection and blood samples were collected from the heart for determination of the levels of serum alanine aminotransferase （ALT）, aspartate transaminase （AST）, tumor necrosis factor-a （TNF- a） and interlukin-1β （IL-1β）. The animals were then sacrificed and lungs removed for determination of glutathione peroxidase （GSH-Px） and superoxide dismutase （SOD） activities, malonodialdehyde （MDA） content and expression of HO-1 mRNA in lung tissues. The left 10 rats in each group were chosen and the survival rates within 72 h after LPS administration were recorded. Results Compared with C group, the levels of serum ALT, AST, TNF-a and IL-1β and MDA content in lung tissues were significantly increased, and GSH-Px and SOD activities in lung tissues and survival rates were decreased in LPS, IL-10, Co and Zn groups （ P 〈 0.05）. Compared with LPS group, the levels of serum ALT, AST, TNF-a, IL-Iβ and MDA content in lung tissues were significantly decreased, GSH-Px and SOD activities in lung tissues and survival rates were increased, and the expression of HO-1 mRNA Was up-regulated （ P 〈 0.05）. Compared with IL-10 group, the levels of serum ALT, AST, TNF-a and IL- lβ and MDA content in lung fissues were significantly increased, and GSH-Px and SOD activities in lung tissues and survival rates were decreased in group Zn （ P 〈 0.05）, and no significant change in the parameters mentioned above was found in Co group （ P 〉 0.05 ） .Conclusion IL-10 can attenuate LPS-induced liver injury in rats by inducing the expression of HO-1.