• 大連醫(yī)科大學(xué)附屬第一醫(yī)院普外科(大連116011);

目的探討p38蛋白激酶（p38 MAPK）在小腸移植早期排斥反應(yīng)中腸黏膜上皮細(xì)胞凋亡機(jī)理中的作用。
方法選用近交系SD和Wistar大鼠進(jìn)行節(jié)段性小腸移植，實(shí)驗(yàn)分3組： 同基因移植組（Wistar→Wistar組）、異基因移植組（SD→Wistar組）和異基因移植加環(huán)孢素A組（SD→Wistar+CsA組）。分別于移植術(shù)后1、3、5及7 d采集移植腸管行病理學(xué)檢查排斥反應(yīng)，TUNEL法檢測凋亡細(xì)胞，并行Westernblotting測定p38 MAPK表達(dá)； 同時(shí)，ELISA法測定血清TNFα活性。
結(jié)果SD→Wistar組腸黏膜上皮細(xì)胞發(fā)生輕、中、重度排斥反應(yīng)中存在細(xì)胞凋亡，凋亡細(xì)胞數(shù)隨排斥反應(yīng)的加重而增加（P＜0.01）； Wistar→Wistar組排斥反應(yīng)輕微，凋亡細(xì)胞數(shù)無明顯變化（P gt;0.05）； SD→Wistar+CsA組隨著CsA的應(yīng)用，排斥反應(yīng)逐漸得到控制，且凋亡細(xì)胞數(shù)也隨著減少。SD→Wistar組及SD→Wistar+CsA組的血清TNFα隨移植腸管上皮細(xì)胞凋亡的輕重而發(fā)生相應(yīng)的變化（P＜0.01）。p38 MAPK在SD→Wistar組隨凋亡細(xì)胞數(shù)增加而表達(dá)加強(qiáng)（P＜0.01），Wistar→Wistar組p38 MAPK表達(dá)無明顯變化（P gt;0.05），在SD→Wistar+CsA組隨凋亡細(xì)胞數(shù)而發(fā)生相應(yīng)的變化（P＜0.01）。小腸移植早期排斥反應(yīng)中腸黏膜上皮細(xì)胞凋亡現(xiàn)象與p38 MAPK呈正相關(guān)（r=0.875，P＜0.01），血清TNFα與移植腸上皮細(xì)胞凋亡呈正相關(guān)（r=0.837, P＜0.01），血清TNFα與p38 MAPK亦呈正相關(guān)（r=0.826，P＜0.01）。
結(jié)論大鼠小腸移植排斥反應(yīng)中存在腸黏膜上皮細(xì)胞凋亡現(xiàn)象，p38 MAPK參與細(xì)胞凋亡信號(hào)轉(zhuǎn)導(dǎo)過程并起重要作用。

引用本文： 張健,胡祥. p38蛋白激酶在小腸移植后腸黏膜上皮細(xì)胞凋亡機(jī)理中的作用. 中國普外基礎(chǔ)與臨床雜志, 2006, 13(1): 66-70. doi: 復(fù)制

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2. Krams SM, Hayashi M, Fox CK, et al. CD8+ cells are not necessary for allograft rejection or the induction of apoptosis in an experimental model of small intestinal transplantation [Ｊ]. J Immunol, 1998; 160(8)∶3673.
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5. Lomo J, Blomhoff HK, Beiske K, et al. TGFbeta 1 and cyclic AMP promote apoptosis in resting human B lymphocytes [Ｊ]. J Immunol, 1995; 154(4)∶1634.
6. Smyth MJ, Trapani JA. Granzymes: exogenous proteinases that induce target cell apoptosis [Ｊ]. Immunol Today, 1995; 16(4)∶202.
7. Kerr JF, Winterford CM, Harmon BV. Apoptosis. Its significance in cancer and therapy [Ｊ]. Cancer, 1994； 73(8)∶2013.
8. Ogawa N, Dang H, Talal N. Apoptosis and autoimmunity [Ｊ]. J Autoimmun, 1995; 8(1)∶1.
9. Raff MC, Barres BA, Burne JF, et al. Programmed cell death and the control of cell survival: lessons from the nervous system [Ｊ]. Science, 1993; 262(5134)∶695.
10. Cerwenka A, Kovar H, Majdic O, et al. Fas and activationinduced apoptosis are reduced in human T cells preactivated in the presence of TGFbeta 1 [Ｊ]. J Immunol, 1996; 156(2)∶459.
11. Wei S, Liu JH, EplingBurnette PK, et al. Critical role of Lyn kinase in inhibition of neutrophil apoptosis by granulocytemacrophage colonystimulating factor [Ｊ]. J Immunol, 1996; 157(11)∶5155.
12. Han J, Lee JD, Bibbs L, et al. A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells [Ｊ]. Science, 1994; 265(5173)∶808.
13. 姜勇， 劉愛華， 張琳， 等. 脂多糖激活p38在誘導(dǎo)腫瘤壞死因子α基因表達(dá)中的作用 [Ｊ]. 中華醫(yī)學(xué)雜志， 1999； 79（5）∶360.
  1. 1. Lee RG, Tsamandas AC, AbuElmagd K, et al. Histologic spectrum of acute cellular rejection in human intestinal allografts [Ｊ]. Transplant Proc, 1996; 28(5)∶ 2767.
  2. 2. Krams SM, Hayashi M, Fox CK, et al. CD8+ cells are not necessary for allograft rejection or the induction of apoptosis in an experimental model of small intestinal transplantation [Ｊ]. J Immunol, 1998; 160(8)∶3673.
  3. 3. Schmid T, Oberhuber G, Korozsi G, et al. Histologic pattern of small bowel allograft rejection in the rat. Mucosal biopsies do not provide sufficient information [Ｊ]. Gastroenterology, 1989; 96(6)∶1529.
  4. 4. Rosemurgy AS, Schraut WH. Small bowel allografts. Sequence of histologic changes in acute and chronic rejection [Ｊ]. Am J Surg, 1986; 151(4)∶470.
  5. 5. Lomo J, Blomhoff HK, Beiske K, et al. TGFbeta 1 and cyclic AMP promote apoptosis in resting human B lymphocytes [Ｊ]. J Immunol, 1995; 154(4)∶1634.
  6. 6. Smyth MJ, Trapani JA. Granzymes: exogenous proteinases that induce target cell apoptosis [Ｊ]. Immunol Today, 1995; 16(4)∶202.
  7. 7. Kerr JF, Winterford CM, Harmon BV. Apoptosis. Its significance in cancer and therapy [Ｊ]. Cancer, 1994； 73(8)∶2013.
  8. 8. Ogawa N, Dang H, Talal N. Apoptosis and autoimmunity [Ｊ]. J Autoimmun, 1995; 8(1)∶1.
  9. 9. Raff MC, Barres BA, Burne JF, et al. Programmed cell death and the control of cell survival: lessons from the nervous system [Ｊ]. Science, 1993; 262(5134)∶695.
  10. 10. Cerwenka A, Kovar H, Majdic O, et al. Fas and activationinduced apoptosis are reduced in human T cells preactivated in the presence of TGFbeta 1 [Ｊ]. J Immunol, 1996; 156(2)∶459.
  11. 11. Wei S, Liu JH, EplingBurnette PK, et al. Critical role of Lyn kinase in inhibition of neutrophil apoptosis by granulocytemacrophage colonystimulating factor [Ｊ]. J Immunol, 1996; 157(11)∶5155.
  12. 12. Han J, Lee JD, Bibbs L, et al. A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells [Ｊ]. Science, 1994; 265(5173)∶808.
  13. 13. 姜勇， 劉愛華， 張琳， 等. 脂多糖激活p38在誘導(dǎo)腫瘤壞死因子α基因表達(dá)中的作用 [Ｊ]. 中華醫(yī)學(xué)雜志， 1999； 79（5）∶360.