早期胰岛素泵注对脓毒症大鼠肝损害的影响

The effects of early continuing insulin pump infusion on liver injury in septic rats

目的探讨早期胰岛素泵注对脂多糖(LPS)致大鼠脓毒症模型肝损害的保护作用。方法24只SD大鼠随机分为LPS+生理盐水组、LPS+胰岛素组和生理盐水对照组,各组均为8只。各组大鼠在实验前1d行右颈外静脉置管术。LPS+生理盐水组腹腔注射LPS10mg.kg-1,同时持续静脉泵注生理盐水1mL.h-1;LPS+胰岛素组腹腔注射LPS10mg.kg-1,同时持续静脉泵注胰岛素生理盐水溶液1mL.h-1(胰岛素用量为0.25U.kg-1.h-1)。生理盐水对照组腹腔注射生理盐水10mg.kg-1,同时持续静脉泵注生理盐水1mL.h-1。测定各组腹腔注射LPS或生理盐水前和注射后2、6、12、24h的血糖水平,检测各组腹腔注射LPS或生理盐水后2、6h的血清TNF-α、IL-6水平及24h的血清ALT和AST水平,并观察各组腹腔注射LPS或生理盐水后24h的肝脏组织病理学改变。结果LPS+生理盐水组在腹腔注射LPS后各采样时间点,血糖水平较生理盐水对照组均显著升高(P<0.05)。注射LPS或生理盐水后2和6h,LPS+生理盐水组血清TNF-α和IL-6水平显著高于生理盐水对照组(P<0.05)。注射LPS或生理盐水后24h,LPS+生理盐水组血清ALT和AST水平均较生理盐水对照组显著升高(P<0.05)。LPS+胰岛素组注射LPS后各采样时间点血糖、TNF-α、IL-6、ALT及AST水平均显著低于LPS+生理盐水组(P<0.05),LPS+生理盐水组肝脏病理学检查示局灶性肝细胞坏死,炎性细胞浸润,小叶间静脉充血扩张;LPS+胰岛素组肝脏病理学改变较LPS+生理盐水组明显减轻。结论早期胰岛素静脉泵注可通过抗炎和降低应激性高血糖作用减轻LPS诱导的肝损害。

Objective To study the protective effects of early continuing insulin pump infusion on liver injury and its associated mechanism in lipopolysaccharide-induced endotoxemic rats. Methods 24 SD rats were randomly divided into 3 groups （every rat was performed an external jugular vein catheterization one day before intraperitoneal injection ） ：saline control group （n = 8） ,LPS ＋ saline group （n =8） and LPS ＋ insulin group （n = 8）. Saline control group was given 0.9% saline only. LPS ＋ saline group was intraperitoneally injected lipopolysaccharide （LPS） （ Escherichia cob serotype 0111 ： B4） 10 mg · kg^ -1 , and then was given a pump infusion of 0.9% saline 1 mL· h^-1 LPS ＋ insulin group received a pump infusion of insulin solution 1 mL· h^-1 after being injected LPS 10 mg·kg^-1 intraperitoneally. The dose of insulin was 0.25 U· kg^-1·h^-1. Blood glucose levels were monitored before intraperitoneal injection and 2 hours, 6 hours, 12 hours, 24 hours after intraperitoneal injection. Blood samples were taken 2 and 6 hours after intraperitoneal injection through external jugular vein catheter and the levels of serum TNF-α and IL- 6 were detected by enzyme-linked immunoadsorbent assay （ELISA）. Hepatic injury was evaluated by detecting the levels of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） 24 hours after intraperitoneal injection. And the liver pathological changes were also examined 24 hours after intraperitoneal injection. Results Compared with saline control group, blood glucose levels elevated significantly in LPS ＋ saline group （ P 〈 0.05 ）. In LPS ＋ insulin group, the levels of blood glucose dropped significantly compared with LPS ＋ saline group （ P 〈 0.05 ） and maintained at normal level. In LPS ＋ saline group, the levels of serum TNF-α and IL-6 elevated significantly compared with saline control group （ P 〈 0.05 ）. And the levels of serum ALT and AST in LPS ＋ saline group were also significantly higher than that in saline control group （ P 〈 0.05 ）. In LPS ＋ insulin group, the levels of serum TNF-α and IL-6 dropped significantly compared with LPS ＋ saline group （ P 〈 0.05 ）. And the levels of serum ALT and AST in LPS ＋ insulin group also dropped significantly compared with LPS ＋ saline group （ P 〈 0. 05 ）. In LPS ＋ saline group, the liver pathological examination showed that LPS could cause hepatocyte edema, liver focal necrosis, inflammatory cell infiltration in portal area and severe congestion of interlobular veins. The pathological examination of LPS ＋ insulin group showed the damage of liver tissue was improved compared with LPS ＋ saline group. Conclusions Early continuing insulin pump infusion can protect liver injury induced by LPS. This effect may be related to attenuating inflammatory reaction and reducing the blood glucose level by insulin.