内毒素血症大鼠肠组织免疫分子的变化及通腑颗粒的干预作用

目的:探讨内毒素血症时大鼠肠组织免疫分子的改变及中药通腑颗粒对其的影响.方法:120只♂Wistar大鼠随机分为正常对照(A)组、内毒素血症(B)组及中药治疗(C)组,各组按造模后预设的取材时间点(2、6、12、24h)分为4小组.通过尾静脉注射的方法建立内毒素血症模型,采用酶联免疫吸附(ELISA)法及放射免疫分析的方法,检测肠组织中的免疫分子及肠内容物中的分泌性免疫球蛋白(sIgA).结果:A、C组INF-γ含量在24h明显高于B组(32.93ng/L±13.17ng/L,37.14ng/L±6.70ng/Lvs23.21ng/L±8.65ng/L,均P<0.05),C组INF-γ含量在12h明显高于A组(39.96ng/L±8.26ng/Lvs29.64ng/L±10.78ng/L,P<0.05).A、C组IL-4含量在6h明显高于B组(115.56ng/L±17.67ng/L,124.39ng/L±26.02ng/Lvs83.36ng/L±27.24ng/L,P<0.05或0.01),但B组IL-4含量在24h较A组明显升高(107.96ng/L±10.86ng/Lvs92.21ng/L±17.62ng/L,P<0.05).B组Foxp3含量在12、24h较A组明显增加(0.28g/L±0.037g/Lvs0.24g/L±0.041g/L;0.26g/L±0.029g/Lvs0.22g/L±0.041g/L,均P<0.05),C组Foxp3含量24h明显低于B组(0.23g/L±0.030g/Lvs0.26g/L±0.029g/L,P<0.05).A、C组sIgA含量2、12、24h明显高于B组(2.43×10-11±0.23×10-11,2.18×10-11±0.27×10-11vs1.66×10-11±0.25×10-11;2.76×10-11±0.22×10-11,2.64×10-11±0.22×10-11vs2.09×10-11±0.20×10-11;2.48×10-11±0.31×10-11,2.25×10-11±0.44×10-11vs1.88×10-11±0.45×10-11,均P<0.05),C组与A组进行对比在2h明显降低.结论:内毒素血症时肠黏膜损伤,肠道产生sIgA减少,肠组织中抑炎因子IL-4先减少后增多,Foxp3增多,而促炎因子INF-γ减少,肠免疫功能发生由炎症反应向抗炎反应的转变,免疫功能出现抑制.应用中药通腑颗粒可以减轻肠黏膜损伤,双向调节炎症反应,保护肠免疫功能.

Clinical and molecular analysis of hereditary non-polyposis colorectal cancer in Chinese colorectal cancer patients

AIM： To analyze the frequency of hereditary non-polyposis colorectal cancer （HNPCC） in Chinese colorectal cancer （CRC） patients, and to discuss the value of microsatellite instability （MSI） and/or immunohistochemistry （IHC） for MSH2/MLH1 protein analysis as pre-screening tests in China. METHODS： The Amsterdam criteria Ⅰ and Ⅱ （clinical diagnosis） and/or germline hMLHI/hMSH2 mutations （genetic diagnosis） were used to classify HNPCC families. Genetic tests, including microsatellite instability, immunohistochemistry for MSH2/MLH1 proteins and hMSH2/hMLH1 genes, were performed in each proband. RESULTS： From July 2000 to June 2004, 1988 patients with colorectal cancer were analysed and 114 CRC patients （5.7%） from 48 families were categorized as having HNPCC, including 76 from 26 families diagnosed clinically and 38 from the other 22 families diagnosed genetically. The sensitivity and specificity of high MSI and IHC for predicting mutations were 100% and 54%, and 79% and 77%, respectively. CONCLUSION： The frequency of HNPCC is approximately 10% among all Chinese CRC cases. The MSI and IHC detections for hMSH2/hMLH1 proteins are reliable prescreening tests for hMLHI/hMSH2 germline mutations in families suspected of having HNPCC.