肝硬化患者血清中基質金屬蛋白酶—3、基質金屬蛋白組織抑制因子—1水平與肝硬化進程的研究

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[摘要] 目的 探討肝硬化患者血清中的基質金屬蛋白酶-3（MMP-3）和基質金屬蛋白組織抑制因子-1（TIMP-1）值對于肝硬化進程的影響。 方法 分析臺州恩澤醫(yī)療集團路橋醫(yī)院2011年1月～2012年6月收治的30例乙型肝炎后肝硬化代償期患者（代償組）及30例失代償期患者（失代償組）的臨床資料，30名健康者作為正常對照組。采用BAS-ELISA法測定MMP-3的血清含量，同時采用ELISA雙抗體夾心法測定TIMP-3的濃度；計算TIMP-1/MMP-3的比值。對比兩組患者的MMP-3、TIMP-1的臨床指標的異同。 結果 ①代償組患者血清MMP-3水平[（20.32±3.10）ng/mL]顯著高于正常對照組血清MMP-3水平[（17.45±2.30）ng/mL]，差異有統(tǒng)計學意義（P < 0.05）；代償組患者血清TIMP-1水平[（1.72±0.40）ng/mL]顯著高于正常對照組[（1.49±0.30）ng/mL]，差異有統(tǒng)計學意義（P < 0.05）；代償組TIMP-1/MMP-3值為（0.088±0.010），比正常對照組TIMP-1/MMP-3值（0.086±0.010）有所升高，但差異無統(tǒng)計學意義（P > 0.05）。②失代償組患者血清MMP-3水平[（22.73±5.20）ng/mL]顯著高于正常對照組[（17.45±2.30）ng/mL]，差異有統(tǒng)計學意義（P < 0.05）；失代償組患者血清TIMP-1水平[（2.24±0.30）ng/mL]顯著高于正常對照組[（1.49±0.30）ng/mL]，差異有統(tǒng)計學意義（P < 0.05）；失代償組患者TIMP-1/MMP-3值為（0.103±0.020），顯著高于正常對照組（0.086±0.010），差異有統(tǒng)計學意義（P < 0.05）。③失代償組患者血清中MMP-3水平顯著高于代償組患者，差異有統(tǒng)計學意義（P < 0.05）；失代償組患者血清TIMP-1水平顯著高于代償組患者，差異有統(tǒng)計學意義（P < 0.05）；失代償組患者TIMP-1/MMP-3值顯著高于代償組患者，差異有統(tǒng)計學意義（P < 0.05）。 結論 代償期肝硬化患者MMP-3以及TIMP-1皆顯著升高，TIMP-1/MMP-3比值有升高趨勢。失代償期肝硬化患者MMP-3以及TIMP-1皆顯著升高，TIMP-1/MMP-3比值顯著升高。MMP-3/TIMP-1的比值與TIMP-1的表達與肝硬化程度有關。

[關鍵詞] 基質金屬蛋白酶-3；基質金屬蛋白組織抑制因子-1；肝硬化進程；相關性

[中圖分類號] R587.1 [文獻標識碼] A [文章編號] 1673-7210（2014）02（c）-0015-04

Study of serum MMP-3， TIMP-1 levels in liver cirrhosis process

MOU Jianli1 TU Yiwei2

1.Department of Infectious Diseases， Luqiao Hospital of Taizhou Enze Medical Group， Zhejiang Province， Taizhou 318050， China； 2.Department of Respiration， Luqiao Hospital of Taizhou Enze Medical Group， Zhejiang Province， Taizhou 318050， China

[Abstract] Objective To study the influence of serum MMP-3， TIMP-1 levels in liver cirrhosis process. Methods 60 patients， who were treated in Luqiao Hospital of Taizhou Enze Medical Group from January 2011 to June 2012 were selected. The clinical data of 30 patients with hepatitis B and compensating liver cirrhosis were chosen as compensating group， 30 patients with decompensating liver cirrhosis were selected as decompensating group， and 30 healthy people were seen as normal control group. BAS-ELISA was established to determine the concentration of MMP-3 in serum， and double antibody sandwich ELISA was established to determine of the concentration of TIMP-3 and calculate the ratio of TIMP-1/MMP-3. The clinical indicators of MMP-3， TIMP-1 in two groups of patients were compared to find the similarities and differences. Results ①MMP-3 and TIMP-1 level in serum of compensating group [（20.32±3.10）， （1.72±0.40） ng/mL] were higher than those of normal control group [（17.45±2.30）， （1.49±0.30） ng/mL]， the differences were statistically significant （P < 0.05）； the value of TIMP-1/MMP-3 in compensating group （0.088±0.010） were little higher than that in normal control group （0.086±0.010）， but the difference was not statistically significant （P > 0.05）. ②MMP-3 level， TIMP-1 level and the value of TIMP-1/MMP-3 in serum of decompensating group [（22.73±5.20）， （2.24±0.30） ng/mL， （0.103±0.020）] were all higher than those of normal control group [（17.45±2.30）， （1.49±0.30） ng/mL， （0.086±0.010）]， the differences were statistically significant （P < 0.05）. ③MMP-3 level in serum of decompensating group was higher than that in compensating group， the difference was statistically significant （P < 0.05）； TIMP-1 level in serum of decompensating group was higher than that in compensating group， the difference was statistically significant （P < 0.05）； TIMP-1/MMP-3 value in decompensating group was higher than that in compensating group， the difference was statistically significant （P < 0.05）. Conclusion MMP-3 level and TIMP-1 level of compensating liver cirrhosis patients are significantly increased， and there is a trend that the ratio of TIMP-1/MMP-3 will increase. MMP-3 level and TIMP-1 level of decompensating liver cirrhosis patients are significantly increased， the value of MMP-3/TIMP-1 is significantly increased. There is a relationship between the ratio of MMP-3/TIMP-1， the expression of TIMP-1 and the extent of liver cirrhosis.

[Key words] MMP-3； TIMP-1； Liver cirrhosis； Correlation

肝硬化的發(fā)生是由相當復雜的細胞與各種酶系之間的相互影響、相互作用引起的，其可因一種或多種因素導致肝臟損傷，肝臟呈纖維性、彌漫性、進行性病變[1]。肝臟出現(xiàn)纖維化的主要病理學進程包括肝細胞外基質的體內合成表達量逐漸增加，而其分解速率卻緩慢降低從而導致肝細胞外基質在肝內逐漸沉積[2]。肝細胞外基質的合成過來以及其分解緩慢是由于基質金屬蛋白組織抑制因子（TIMPs）和基質金屬蛋白酶（MMPs）兩種酶系的表達變化引起的。MMPs的作用是促進肝細胞外基質的分解，從而減少肝細胞外基質的含量，降低肝細胞外基質積聚的可能性，從而減小肝纖維化發(fā)生概率，而TIMPs的作用是抑制MMPs活性，進而阻斷細胞外基質的降解，對肝纖維化進程起到了促進的作用，從而推動肝臟組織的肝硬化進程[3-4]。……