摘要目的 探讨姜黄素对脓毒症大鼠肝细胞的保护作用.方法 按随机数字表法将80只健康雄性SD大鼠分为假手术组、脓毒症组、血必净组、姜黄素组,每组20只.采用盲肠结扎穿孔术(CLP)建立脓毒症动物模型;假手术组仅开腹取出盲肠后还纳关腹.血必净组和姜黄素组分别于术后0、8、16 h腹腔注射血必净注射液4 mL/kg、姜黄素100 mg/kg(用生理盐水稀释至4 mL/kg);假手术组和脓毒症组注射等量生理盐水.各组分别于术后2、6、12、24 h取5只大鼠,留取血液和肝组织标本;采用酶联免疫吸附试验(ELISA)检测血清降钙素原(PCT)、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL-6、IL-1β)水平;苏木素-伊红(HE)染色后观察肝组织病理学改变;原位末端缺刻标记法(TUNEL)检测肝组织细胞凋亡情况并计算凋亡指数(AI).结果 脓毒症组肝细胞损伤程度随时间延长逐渐加重,凋亡细胞逐渐增多,肝细胞AI持续升高至24 h达峰值,血清PCT、TNF-α、IL-6和IL-1β水平于术后2 h起即明显高于假手术组,且随时间延长逐渐升高至12 h达峰值.血必净组和姜黄素组镜下观察肝组织损伤程度明显轻于脓毒症组,凋亡细胞明显减少;肝细胞AI及血清PCT、TNF-α、IL-6和IL-1β水平均于术后2 h起明显低于脓毒症组〔AI:2 h为(11.89±1.34)%、(11.56±0.96)%比(23.59±2.00)%,24 h为(28.95±1.40)%、(30.35±1.20)%比(52.05±1.31)%;PCT(μg/L):2 h为1.27±0.18、1.13±0.19比2.41±0.21,12 h为5.07±0.45、5.09±0.42比8.68±0.58;TNF-α(ng/L):2 h为127.93±9.53、124.73±7.47比217.28±14.24,12 h为171.03±8.58、168.68±6.95比314.13±14.39;IL-6(ng/L):2 h为132.15±9.27、136.14±8.42比153.35±12.64,12 h为211.65±8.52、213.37±8.96比298.11±12.35;IL-1β(ng/L):2 h为33.59±1.49、35.05±1.00比61.84±3.21,12 h为81.76±2.80、84.06±3.42比132.24±2.58,均P<0.05〕,且姜黄素组与血必净组各指标比较差异均无统计学意义(均P>0.05).结论 姜黄素能抑制脓毒症大鼠肝细胞炎症反应,减少肝细胞凋亡,对脓毒症肝细胞损伤起到保护作用.

abstractsObjective To investigate the protective effect of curcumin on hepatocytes in rats with sepsis. Methods Eighty healthy male Sprague-Dawley (SD) rats were randomly divided into sham operation group, sepsis group, Xuebijing group and curcumin group (20 rats in each group) according to the random number table method. The animal model of sepsis was established by cecal ligation and puncture (CLP). In the sham operation group, the cecum was removed only after the operation. The rats in Xuebijing group and curcumin group were injected with 4 mL/kg Xuebijing, 100 mg/kg curcumin intraperitoneally at 0, 8 and 16 hours after operation (diluted with normal saline to 4 mL/kg) respectively; Sham operation group and sepsis group were injected with the same volume of normal saline. Five rats in each group were sacrificed at 2, 6, 12 and 24 hours after operation, the blood sample was collected, and liver tissues were harvested. The levels of serum procalcitonin (PCT), tumor necrosis factor-α (TNF-α) and interleukin (IL-6, IL-1β) were measured by enzyme linked immunosorbent assay (ELISA), the pathological changes of liver tissues were observed by hematoxylin-eosin (HE) staining, and apoptosis index (AI) was measured by TdT-mediated dUTP nick end labeling (TUNEL) method.Results The degree of hepatocyte injury in sepsis group increased gradually with time, the apoptotic cells gradually increased, and the AI of liver cells increased to 24 hours; serum levels of PCT, TNF-α, IL-6 and IL-1β were significantly higher than those in the sham operated group at 2 hours after operation and gradually increased to peak at 12 hours. The injury degree of liver tissue in Xuebijing group and curcumin group was significantly lighter than that in sepsis group, and the number of apoptotic cells were significantly decreased; the AI of hepatocytes and serum levels of PCT, TNF-α, IL-6 and IL-1β were significantly lower than those of sepsis group from 2 hours [AI: (11.89±1.34)%, (11.56±0.96)% vs. (23.59±2.00)% at 2 hours, (28.95±1.40)%, (30.35±1.20)% vs. (52.05±1.31)% at 24 hours; PCT (μg/L): 1.27±0.18, 1.13±0.19 vs. 2.41±0.21 at 2 hours, 5.07±0.45, 5.09±0.42 vs. 8.68±0.58 at 12 hours; TNF-α (ng/L): 127.93±9.53, 124.73±7.47 vs. 217.28±14.24 at 2 hours, 171.03±8.58,&nbsp;168.68±6.95 vs. 314.13±14.39 at 12 hours; IL-6 (ng/L): 132.15±9.27, 136.14±8.42 vs. 153.35±12.64 at 2 hours, 211.65±8.52, 213.37±8.96 vs. 298.11±12.35 at 12 hours; IL-1β (ng/L): 33.59±1.49, 35.05±1.00 vs. 61.84±3.21 at 2 hours; 81.76±2.80, 84.06±3.42 vs. 132.24±2.58 at 12 hours, allP < 0.05]. There was no significant difference in the above indexes between Xuebijing group and curcumin group.ConclusionCurcumin can inhibit the inflammatory response of hepatocytes in sepsis rats and reduce the apoptosis of hepatocytes, which can protect hepatocytes from sepsis.