虾青素对脓毒症小鼠器官功能及炎症因子的影响及作用
Astaxanthin pretreatment improves sepsis-induced organ dysfunction and inhibits inflammatory factors release in mice

摘要：目的 观察虾青素(astaxanthin, ASX)预处理对脓毒症小鼠器官功能及死亡率的影响。方法 采用小鼠盲肠结扎穿孔(cecal ligation and puncture, CLP)法诱导脓毒症。小鼠按随机数字表法分为空白对照组、脓毒症组(CLP组)及虾青素预处理组[CLP+ASX组，CLP造模前以剂量60mg/(kg？d)ASX连续灌胃14d]。观察各组小鼠CLP术后：①72h(术后每天仍以上述剂量灌胃)的存活率；②24h统计各组小鼠的临床评分，处死小鼠后取小鼠的血液标本检测血清中谷丙转氨酶(ALT)、血尿素氮(BUN)、肿瘤坏死因子-α(TNF-α)及白介素-6(IL-6)的水平，取小肠、肺脏、肝脏及肾脏组织用以检测各主要脏器的功能及病理变化。结果 与CLP组比较，CLP+ASX组小鼠的72h死亡率显著降低(P=0.0202)。CLP造模24h后，CLP+ASX组小鼠的临床评分明显低于CLP组(10.78±0.79 vs.13.67±0.44，P=0.005)。通过血清生化指标及组织的病理学分析，CLP+ASX组小鼠的小肠[小鼠肠绒毛的高度：(390.67±14.58)μm vs. (326.67±10.31)μm，P=0.005]、肺脏(肺组织的湿重/干重比：4.75±0.24 vs.5.05±0.22，P=0.0476)、肝脏[血清ALT：(105.0±10.53)U/L vs. (174.8±9.289)U/L，P=0.0006]及肾脏组织[BUN：(54.50±？？3.57？？)mg/dL vs. (69.17±3.33)mg/dL，P=0.0132]的功能及病理损伤明显轻于CLP组。同时ASX也可以显著抑制脓毒症时炎症因子TNF-α[(258.06±16.21)pg/mL vs. (538.17±30.80)pg/mL，P<0.0001]及IL-6[(5.90±0.80)ng/mL〖JP〗 vs. (12.56±0.55)ng/mL，P<0.0001]的释放。结论 ASX预处理能够显著降低脓毒症小鼠的死亡率，抑制炎症因子的释放并对重要器官功能具有保护作用。
ABSTRACT: Objective To investigate the therapeutic role and potential mechanisms of astaxanthin (ASX) pretreatment on cecal ligation and puncture (CLP)-induced sepsis in mice. Methods Sepsis was induced by CLP in male mice, which were then randomly divided into saline control group, sepsis model group (CLP group), and CLP+ASX group (mice received 60mg/(kg？d) ASX dissolved in olive oil via oral gavage for 14 consecutive days before CLP operation). ① The mice were monitored to assess 72-hour survival rate. ② Clinical scores of mice in the three groups were calculated 24h after CLP to determine the severity of sepsis. Blood samples were collected at 24h after CLP modeling to determine the serum ALT, BUN, TNF-α and IL-6 levels. The intestine, lung, liver and kidney tissues were collected to assess organ functions and pathological changes. Results The results showed that mice in CLP group had a significantly lower survival rate at 72h than those in CLP+ASX group (P=0.0202). CLP+ASX sepsis group had a lower clinical score than CLP sepsis group(10.78±0.79 vs. 13.67±0.44, P=0.005). The tissue histopathology and biochemical analysis revealed that ASX markedly alleviated histological examination damage in the intestines [villus height: (390.67±14.58)μm vs. (326.67±10.31)μm, P=0.005], lung (lung wet/dry ratio: 4.75±0.24 vs. 5.05±0.22, P=0.0476), liver [ALT: (105.0±10.53)U/L vs. (174.8±9.289)U/L, P=0.0006] and kidney [BUN: (54.50±3.57)mg/dL vs. (69.17±3.33)mg/dL, P=0.0132] tissues in sepsis. Moreover, significant lower levels of TNF-α [(258.06±16.21)pg/mL vs. (538.17±30.80)pg/mL, P<0.0001] and IL-6 [(5.90±0.80)ng/mL vs. (12.56±0.55)ng/mL, P<0.0001] were