目的 探讨姜黄素对内毒素诱导大鼠脓毒症所造成脏器损伤的保护机制.方法清洁级Wistar雄性大鼠60只,随机分为空白对照组12只,脓毒症模型组(模型组)24只,姜黄索治疗组(治疗组)24只.腹腔注射脂多糖5 mg/kg制成脓毒症大鼠模型.治疗组在造模后立即给予尾静脉注射姜黄素50mg/kg处理.实验开始后4、8、12和24 h从下腔静脉分别取血测定血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、肌酐(Cre)、血尿素氮(BUN)、白介素-18(IL-18)及肿瘤坏死因子-α(TNF-α);取肝、肾组织标本进行病理组织学观察.结果模型组比较对照组的ALT、AST、Cre、BUN水平在各时间点均明显升高(P<0.01),均在8 h达到最高峰;IL-18及TNF-α水平在4、8、12 h均明显升高(P<0.01),均在8 h达到最高峰,24 h差异无统计学意义(P>0.05).治疗组比较模型组的ALT、AST、Cre、BUN、IL-18水平在各时间点均明显下降(P<0.05);TNF-α水平在4、8、12 h均明显下降(P<0.05),24 h差异无统计学意义(P>0.05).模型组的肝组织病理改变主要为弥漫空泡变性,散在嗜酸性变性,肝窦内散在急慢性炎细胞浸润,肝细胞灶性坏死,小脓肿形成.肾组织病理改变主要为肾小球弥漫嗜中性粒细胞浸润,部分肾小球节段性坏死,球囊扩张,肾小管上皮弥漫刷状缘脱落,部分管型形成,局部重度空泡变性.肝、肾组织病理改变均以8 h为最重,与血清中的生化和免疫指标变化趋势相符.治疗组的肝肾组织病理改变明显较模型组减轻.结论脓毒症可以造成急性肝、肾损伤,IL-18可以作为判断脓毒症造成脏器损伤的特异性指标.姜黄素能够抑制脓毒症大鼠IL-18、TNF-α的过度产生,从而减轻脓毒症中过度的炎症反应,以发挥其保护脓毒症所造成的脏器损伤的作用.%Objective To investigate the protective mechanisms of Curcumin on organ injury caused by LPS-induced sepsis in rats. Methods Sixty Wister male rats were randomly divided into tliree groups: the control group (C group. .0=12), the LPS-induced sepsis group (LPS group, n=24), the Curcumin treatment group (LPS+Cur group, n=24). Sepsis was induced by iniraperitoneal injection of 5 nig/kg LPS. The LPS I Cur group was injected with 50 mg/kg curcumin, immediately followed by intraperitoneal LPS injection. At 4, 8. 32 and 2-1 h after the start, of experiment, blood was obtained from the inferior vena eava of rats and serum ALT, AST, Cre, BUN, 1L-18 and TNF- a were measured. Then these rats were killed by cervical dislocation at each time point and their liver and kidney tissues were kept for histological examination. Results Compared with the C group, ALT, AST, Cre and BUN levels of the LPS group were significantly increased at each time point (i'<0.01) and peaked at 8 h; 1L-18 and TNF- a levels of the LPS group were significantly increased at 4, 8, 12 h (P<0.01) and both peaked at 8 h while no significance was obscrtved at 24 h (P>0.05). Compared with the LPS group, ALT. AST, Cre. BUN, TL-i 8 levels of the LPS Cur group were significantly decreased at each time point (P＜0.05); TNF- a levels of the LPS+Cur group were significantly decreased at A, 8, 12 h (P<0.05) while no significance was observed at 24 h (P>0.05). Pathological changes in liver tissues of the LPS group were mainly diffuse vacuolar degeneration, scattered eosinophilic degeneration, scattered acute and chronic inflammatory cells infiltration of hepatic sinusoids, focal necrosis of liver cells, small abscess formation. Pathological changes in kidney tissues were mainly diffuse infiliitration of neutrophils in giomerular, part of segmental glomerular necrosis, balloon dilatation, diffuse tubular brushborder loss, part of the tube formation, local severe vacuolar degeneration. Pathological changes in liver and kidney tissues were the severest at 8 h, which was in agreement with serum biochemical and immune parameters. Pathological changes in liver and kidney tissues of the LPS+Cur group were significantly ameliorated when compared with, the LPS group. Conclusions Sepsis can cause acute liver and kidney damage. 1L,-18 cart be used to determine otgan damage caused by sepsis as a detection marker. Curcumin can protect organ function from injury caused by sepsis because it can inhibit exeessive production of'TNF- a and TL-18 and reduce the excessive inflammatory response in sepsis.
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