口服MHC-CTB交联物对大鼠移植肾存活的影响

The effect of MHC-CTB cross-linking agent administrated orally on kidney allograft survival in rats

目的观察口服MHC-CTB交联物对大鼠肾移植术后的影响。方法用固相法合成MHC肽,对其相对分子质量和纯度进行检测后,口服MHC-CTB交联物灌胃2次/周,持续2个月;对照组口服灌胃生理盐水为对照,以BN(RT1n)大鼠为供体,Lewis(RT11)大鼠为受体,建立大鼠肾移植模型,观察两组术后外周血CD4+CD25+T细胞含量变化、两组生存时间、移植肾病理变化情况,并在体外试验中,通过混合淋巴细胞培养,进一步验证,MHC肽对T淋巴细胞有无抑制其增殖功能。结果通过固相法合成的MHC肽相对分子质量为1 389.81,纯度为98.1%,建立大鼠肾移植模型后,术后第1天外周血流式结果显示实验组CD4+CD25+T细胞较对照组明显升高(P<0.01),且实验组生存天数为(21.4±1.45)d,对照组生存天数为(8.2±2.15)d,二者间比较差异有统计学意义(P<0.01),移植肾病理切片显示对照组移植肾排斥变化早于实验组,体外混合淋巴细胞培养显示,实验组T淋巴细胞增殖弱于对照组(P<0.01),且添加MHC肽后,T淋巴细胞增殖抑制效果更明显(P<0.01)。结论口服MHC肽能有效诱导免疫耐受,抑制大鼠肾移植排斥,延长生存时间。

Objective To observe the effect of MHC-CTB cross-linking agent administrated orally on kidney allograft survival in rats.Methods Synthesizing MHC peotides by using solid phase method,its molecular weight and purity were dectected.Oral tolerance was induced by intragastric administration（gavage） at a dose of 5 mg/kg twice weekly until day 60,while rats in control group feed with 1 mL physiological saline as conrol.BN（RT1n） and Lewis（RT11） were chosed as donors and receipents,the allogenic kidney transplantation was performed,then the assays of CD4＋CD25＋T cells in peripheral blood;the survival time and the pathological of kidney allograft was observed.The function of MHC inhibition to the proliferation of T cells was further observed by mix lymphocyte culture.Results The molecular weight and purity of MHC peptide was 1 389.81 and 98.1% respectively.The assays of CD4＋CD25＋ T cells in peripheral blood were increased in experiment group at day 1 post-transplantation（P〈0.01）;the survival time of kidney allografts in experiment group and control group were（21.4±1.45）d and（8.2±2.15）d respectively（P〈0.01）.And transplantation kindey HE showed acute rejection happened earlier in the control.In vitro,the proliferation of T cells were inhibited and the effect of inhibition was highly increased by adding MHC peptides（P〈0.01）.Conclusion Oral adminsitration of MHC peptides can induce immune tolerance,inhibit the rejeciton of allograft kindey and prolong the survival time of kidney allografts.