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门静脉高压症脾功能亢进患者脾脏巨噬细胞Toll样受体4的表达及意义

[Expression and significance of Toll-like receptor 4 of splenic macrophage in patients with hypersplenism due to portal hypertension].

作者信息

Li Zong-Fang, Zhang Yu, Gao Jun, Zhang Pan-Jian, Wang Ji-Xin, Liu Xiao-Gong

机构信息

Department of General Surgery, The Second Hospital of Xi'an Jiaotong University, Xi'an 710004, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2004 Jul 2;84(13):1088-91.

PMID:15312508
Abstract

OBJECTIVE

To observe the change in expression of Toll-like receptor 4 (TLR4) of splenic macrophage in patients with hypersplenism due to portal hypertension (PH), and investigate the role of TLR4 of splenic macrophage in hypersplenism.

METHODS

Splenectomy was performed on 20 patients with hypersplenism due to PH (hypersplenism group) and 6 patients with rupture of spleen by trauma (control group) and the specimens of spleen were collected. The splenic macrophages were isolated by adhibit wall method. The expression of TLR4 of splenic macrophage was detected by immunohistochemical method (SABC), and the result was analyzed by the image analysis system. The phagocytosis of splenic macrophage was measured by chicken red blood cell (CRBC) phagocytosis assay. The level of serum endotoxin was detected before the operation by limulus assay. The results of these 2 groups were compared, and correlation analysis was made among different results of the hypersplenism group.

RESULTS

The expression of TLR4 of splenic macrophage was 109 +/- 32 in the hypersplenism group, significantly higher than that of the control group (62 +/- 5, P < 0.01). The rate of phagocytosis and index of phagocytosis of splenic macrophage in the hypersplenism group were 12.6% +/- 3.0% and 0.146 +/- 0.035 respectively, both significantly higher than those of the control group (6.9% +/- 0.5% and 0.076 +/- 0.008 respectively, both P < 0.01) The level of endotoxin of the hypersplenism group was 0.28 EU/ml +/- 0.21 EU/ml, significantly higher than that of the control group (0.054 EU/ml +/- 0.014 EU/ml, P < 0.05). The rate of phagocytosis and the index of phagocytosis of splenic macrophage were notably positively correlated with the expression of TLR4 (r = 0.601, P < 0.01 and r = 0.553, P < 0.05), and the level of endotoxin (r = 0.724 P < 0.01 and r = 0.506, P < 0.05). The expression of TLR4 of splenic macrophage was positively correlated with the level of endotoxin (r = 0.525, P < 0.05).

CONCLUSION

The expression of TLR4 of splenic macrophage in patients with hypersplenism due to PH was increased significantly. It may be one of the important factors of hypersplenism due to PH that "endotoxemia-->increase of expression of TLR4 of splenic macrophage (activation of TLR of splenic macrophage)-->increased destruction of red blood cells by macrophage".

摘要

目的

观察门静脉高压(PH)所致脾功能亢进患者脾巨噬细胞Toll样受体4(TLR4)表达的变化,探讨脾巨噬细胞TLR4在脾功能亢进中的作用。

方法

对20例PH所致脾功能亢进患者(脾功能亢进组)及6例外伤性脾破裂患者(对照组)行脾切除术并采集脾脏标本。采用贴壁法分离脾巨噬细胞。采用免疫组织化学法(SABC法)检测脾巨噬细胞TLR4的表达,并通过图像分析系统进行结果分析。采用鸡红细胞(CRBC)吞噬试验检测脾巨噬细胞的吞噬作用。术前采用鲎试剂法检测血清内毒素水平。比较两组结果,并对脾功能亢进组不同结果进行相关性分析。

结果

脾功能亢进组脾巨噬细胞TLR4表达为109±32,显著高于对照组(62±5,P<0.01)。脾功能亢进组脾巨噬细胞吞噬率和吞噬指数分别为12.6%±3.0%和0.146±0.035,均显著高于对照组(分别为6.9%±0.5%和0.076±0.008,P均<0.01)。脾功能亢进组内毒素水平为0.28 EU/ml±0.21 EU/ml,显著高于对照组(0.054 EU/ml±0.014 EU/ml,P<0.05)。脾巨噬细胞吞噬率和吞噬指数与TLR4表达显著正相关(r=0.601,P<0.01;r=0.553,P<0.05),与内毒素水平也显著正相关(r=0.724,P<0.01;r=0.506,P<0.05)。脾巨噬细胞TLR4表达与内毒素水平正相关(r=0.525,P<0.05)。

结论

PH所致脾功能亢进患者脾巨噬细胞TLR4表达显著增加。“内毒素血症→脾巨噬细胞TLR4表达增加(脾巨噬细胞TLR活化)→巨噬细胞对红细胞破坏增加”可能是PH所致脾功能亢进的重要因素之一。

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