内毒素血症大鼠中库普弗细胞介导的肠道损伤。
Intestinal damage mediated by Kupffer cells in rats with endotoxemia.
作者信息
Gong Jian-Ping, Wu Chuan-Xin, Liu Chang-An, Li Sheng-Wei, Shi Yu-Jun, Yang Kang, Li Yue, Li Xu-Hong
机构信息
Department of General Surgery, The Second College of Clinical Medicine & the Second Affiliated Hospital of Chongqing University of Medical Science, 74 Linjiang Road, Chongqing 400010, China.
出版信息
World J Gastroenterol. 2002 Oct;8(5):923-7. doi: 10.3748/wjg.v8.i5.923.
AIM
To determine the in vivo effects of phagocytic blockade of Kupffer cell (KC) on the release of proinflammatory cytokines in small intestinal lesion and on the integrity of intestinal tract by using gadolinium chloride (GdCl(3)) during early endotoxemia.
METHODS
Wistar rats were divided into three groups: Group A, rats were injected with endotoxin (E. coli O111:B(4), a dose of 12 mg x kg(-1)) only; Group B, rats were pretreated intravenously with 25 mg of GdCl(3) per kg 24 h are given endotoxin; and Group C, sham operation only. All animals were sacrificed 4 h after endotoxin injection. In portion of the rats of three groups, bile duct was cannulated, which the bile was collected externally. Morphological changes of ileum were observed under light microscopy and electronic microscopy. The KC were isolated from rats by collagenase perfusion and in KC, expression of TNF-alpha and IL-6 mRNA were determined by RT-PCR analysis. Plasma and bile TNF-alpha and IL-6 Levels were determined by enzyme-linked immunosorbent assay (ELISA).
RESULTS
In group A, there were neutrophil infiltration and superficial epithelial necrosis of the ileal villi, sloughing of mucosal epithelium, and disappearance of some villi. In group B, the ileal mucosal damage was much reduced. which in group C, no significant morphological changes were seen. GdCl(3) pretreatment decreased significantly the expression of TNF-alpha and IL-6 mRNA in group B (4.32+/-0.47 and 4.05+/-0.43) when compared to group A (9.46+/-1.21 and 9.04+/-1.09) (P<0.05). There was no significant expression of TNF-alpha and IL-6 mRNA in group C (1.03+/-0.14 and 10.4+/-0.13). In rats of group A, the levels of TNF-alpha and IL-6 in bile and plasma were 207+/-29 ng x L(-1), 1032+/-107 ng x L(-1), 213+/-33 ng x L(-1), and 1185+/-127 ng x L(-1), respectively. In group B, they were 113+/-18 ng x L(-1), 521+/-76 ng x L(-1), 147+/-22 ng x L(-1), and 572+/-54 ng x L(-1), respectively. In group C, they were 67+/-10 ng x L(-1), 72+/-13 ng x L(-1), 109+/-18 ng x L(-1), and 118+/-22 ng x L(-1) respectively. There were significant difference between the three group (P<0.05).
CONCLUSION
KC release cytokines TNF-alpha and IL-6 causing damage to the integrity of intestinal epithelium and play a crucial role in the initiation and progression of intestinal mucosal damage during early endotoxemia.
目的
通过在内毒素血症早期使用氯化钆（GdCl₃）来确定库普弗细胞（KC）吞噬功能阻断对小肠损伤中促炎细胞因子释放及肠道完整性的体内影响。
方法
将Wistar大鼠分为三组：A组，仅给大鼠注射内毒素（大肠杆菌O111:B₄，剂量为12 mg·kg⁻¹）；B组，每千克体重静脉注射25 mg GdCl₃预处理24小时后给予内毒素；C组，仅进行假手术。内毒素注射4小时后处死所有动物。在三组部分大鼠中，插入胆管以体外收集胆汁。在光学显微镜和电子显微镜下观察回肠的形态学变化。通过胶原酶灌注从大鼠中分离KC，并通过逆转录-聚合酶链反应（RT-PCR）分析测定KC中肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）mRNA的表达。通过酶联免疫吸附测定（ELISA）测定血浆和胆汁中TNF-α和IL-6的水平。
结果
A组中，回肠绒毛有中性粒细胞浸润和浅表上皮坏死，黏膜上皮脱落，部分绒毛消失。B组中，回肠黏膜损伤明显减轻，C组未见明显形态学变化。与A组（9.46±1.21和9.04±1.09）相比，GdCl₃预处理显著降低了B组中TNF-α和IL-6 mRNA的表达（4.32±0.47和4.05±0.43）（P<0.05）。C组中TNF-α和IL-6 mRNA无明显表达（1.03±0.14和1.04±0.13）。A组大鼠胆汁和血浆中TNF-α和IL-6的水平分别为207±29 ng·L⁻¹、1032±107 ng·L⁻¹、213±33 ng·L⁻¹和1185±127 ng·L⁻¹。B组中分别为113±18 ng·L⁻¹、521±76 ng·L⁻¹、147±22 ng·L⁻¹和572±54 ng·L⁻¹。C组中分别为67±10 ng·L⁻¹、72±13 ng·L⁻¹、109±18 ng·L⁻¹和118±22 ng·L⁻¹。三组之间存在显著差异（P<0.05）。
结论
KC释放细胞因子TNF-α和IL-6，导致肠上皮完整性受损，在内毒素血症早期肠道黏膜损伤的起始和进展中起关键作用。
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