N-乙酰半胱氨酸对进展期结直肠癌患者术后机体免疫抑制状态的改善
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摘要
目的通过检测进展期结直肠癌患者手术前后机体CD3+TCR-ζ双阳性T细胞、IL-6、IL-10和IFN-γ等指标水平的变化,说明由于肿瘤本身及手术打击等多重因素影响,进展期结直肠癌患者术后机体呈现出免疫抑制加重的趋势,支持了瘤源性免疫抑制的观点。实验重点是通过术后使用抗氧化剂N-乙酰半胱氨酸(NAC)的治疗,上述检测指标水平发生了变化,术后机体的免疫抑制状态得到改善,从而证实抗氧化剂NAC能够改善进展期结直肠癌患者术后免疫抑制状态。
方法本实验选取了天津市人民医院2006年10月-2006年12月接受根治手术治疗的20名结直肠癌患者,其中男13例,女7例,年龄31～77岁,平均59.9岁。患者入组条件为无放、化疗史,无使用可能影响患者机体免疫状态的药物史。将20名患者随机分成A、B两组,每组10名,A组为对照组,B组为实验组,B组术后第1天起使用NAC静脉输液治疗共7天,剂量为8g/天。A、B两组均于术前、术后第1天、术后第3天及术后第7天取血检测CD3+TCR-ζ双阳性T细胞、IL-6、IL-10和IFN-γ等指标。CD3+TCR-ζ双阳性T细胞使用流式细胞仪采用双色直接免疫荧光法检测,IL-6、IL-10和IFN-γ检测采用酶联免疫吸附实验方法检测。所有数据使用SPSS11.5统计软件进行数据分析,比较手术前后指标变化及两组间指标差异,P＜0.05为差异有统计学意义。
结果从各组检测指标术前术后比较来看:对照组患者术后机体IFN-γ和CD3+TCR-ζ双阳性T细胞的水平较术前有下降趋势,而IL-10水平有升高趋势,在不同检测时间内大部分的差异都具有统计学意义,(P＜0.05)。实验组患者术后机体CD3+TCR-ζ双阳性T细胞的水平较术前有升高趋势,且在术后第3天与术后第7天这种差异有统计学意义,(P＜0.05),这种变化趋势与对照组相反;机体IL-6水平与术前比较有下降趋势,且大部分检测时间内变化有统计学意义;IFN-γ水平虽然与术前比较与对照组一样有下降趋势,但这种差异只在少部分检测时间内有统计学意义;同样术后机体IL-10水平与术前比较升高趋势并不明显,只在术后第3天具有显著差异,(P＜0.05)。从实验组与对照组各检测指标比较来看,实验组患者术后机体IFN-γ和CD3+TCR-ζ双阳性T细胞的水平比对照组高,且大部分检测时间内差异具有统计学意义,(P＜0.05);同样实验组患者术后机体IL-6、IL-10水平在大部分检测时间内较对照组低,差异具有统计学意义,(P＜0.05)。
结论进展期结直肠癌患者术后机体呈现出免疫抑制状态;使用抗氧化剂NAC治疗可以改善这种免疫抑制状态;以8g/天的剂量使用NAC治疗安全性良好,希望为临床治疗进展期结直肠癌提供一条新途径。
Objective Through detecting some indexes such as CD3+TCR-ξbi-positive T-cell, IL-6,IL-10 and IFN-γ,of the patients with progressive colorectal carcinoma perioperatively,we had demonstrated that after operation,the organisms' immune state have aggravated further because of operation coup and other correlation factors, support the view of tumor-source immunosuppressive.These indexes changed after the operation because of the therapy for antioxidant N-acetylcysteine(NAC),the organisms' immune suppression state was amended,this is the emphasis of the experiment,so it confirm that after operation,the antioxidant NAC could amend the organisms' immune suppression state of the patients with progressive colorectal carcinoma.
Method The experiment choose 20 cases in which the patients suffered from colorectal carcinoma and have get radical surgery yet from TIANJIN Union Medicine Centre between October and December in 2006,in which 13 cases were males,7 females,ages from 31 to 77 years old,average 59.9 years.All of them had not accepted radiotherapy or chemical therapy,even any other medicine that can affect immune state.These 20 patients were divided into A and B group,10 cases each group,we took A as control group,and B as experiment group,the patients in B group had get NAC in vein dripping for 7 days after operations,8g everyday.The index including CD3+TCR-ξbi-positive T-cell,IL-6,IL-10 and IFN-γ,were detected both in A and B before operation,the 1st day,the 3rd day,the 7th day after operation respectively.By DIF through flow cytometry to detect CD3+TCR-ξbi-positive T-cell,and by ELISA to detect IL-6,IL-10 and IFN-γ.We use the statistics software SPSSl1.5 to analysis the data,and compare the difference of the index between pro-operation and after the operation,and between A and B group. If P＜0.05 it has statistical significance.
Result In control group IFN-γand CD3+TCR-ξbi-positive T-cell after operation were descended,but IL-10 was step up in most time subtotal distinction possess statistical significance,(P＜0.05).In experiment group CD3+TCR-ξbi-positive T-cell show augmented tendency than before operation,moreover difference in the 3rd and 7th day after operation have statistical significance,(P＜0.05).These changes contrast in control group:compared with IL-6 in most of time the index is lower than control group,distinction shows statistical significance.Although compared with after operation IFN-γdecreases like control group,but only in less time it had statistical significance:as the same the level of IL-10 does not have manifest upright tendency,only in the 3rd after operation show obvious difference, (P＜0.05).Compared experiment group and control group,in experiment group IFN-γand CD3+TCR-ξbi-positive T-cell are higher than in control group,and in most time it possess statistical significance,(P＜0.05);IL-6 and IL-10 after operation are lower than control group in most detecting time and the distinctions possess statistical significance.(P＜0.05.)
Conclusion It discovered that the organisms development immune suppression state in patients with progressive colorectal carcinoma after operation;the therapy of NAC could amend the organisms' immune suppression state;the dose of 8g/day was safety,and we expect that it could offer a new route for progressive colorectal carcinoma in clinical therapy.
方法本实验选取了天津市人民医院2006年10月-2006年12月接受根治手术治疗的20名结直肠癌患者,其中男13例,女7例,年龄31～77岁,平均59.9岁。患者入组条件为无放、化疗史,无使用可能影响患者机体免疫状态的药物史。将20名患者随机分成A、B两组,每组10名,A组为对照组,B组为实验组,B组术后第1天起使用NAC静脉输液治疗共7天,剂量为8g/天。A、B两组均于术前、术后第1天、术后第3天及术后第7天取血检测CD3+TCR-ζ双阳性T细胞、IL-6、IL-10和IFN-γ等指标。CD3+TCR-ζ双阳性T细胞使用流式细胞仪采用双色直接免疫荧光法检测,IL-6、IL-10和IFN-γ检测采用酶联免疫吸附实验方法检测。所有数据使用SPSS11.5统计软件进行数据分析,比较手术前后指标变化及两组间指标差异,P＜0.05为差异有统计学意义。
结果从各组检测指标术前术后比较来看:对照组患者术后机体IFN-γ和CD3+TCR-ζ双阳性T细胞的水平较术前有下降趋势,而IL-10水平有升高趋势,在不同检测时间内大部分的差异都具有统计学意义,(P＜0.05)。实验组患者术后机体CD3+TCR-ζ双阳性T细胞的水平较术前有升高趋势,且在术后第3天与术后第7天这种差异有统计学意义,(P＜0.05),这种变化趋势与对照组相反;机体IL-6水平与术前比较有下降趋势,且大部分检测时间内变化有统计学意义;IFN-γ水平虽然与术前比较与对照组一样有下降趋势,但这种差异只在少部分检测时间内有统计学意义;同样术后机体IL-10水平与术前比较升高趋势并不明显,只在术后第3天具有显著差异,(P＜0.05)。从实验组与对照组各检测指标比较来看,实验组患者术后机体IFN-γ和CD3+TCR-ζ双阳性T细胞的水平比对照组高,且大部分检测时间内差异具有统计学意义,(P＜0.05);同样实验组患者术后机体IL-6、IL-10水平在大部分检测时间内较对照组低,差异具有统计学意义,(P＜0.05)。
结论进展期结直肠癌患者术后机体呈现出免疫抑制状态;使用抗氧化剂NAC治疗可以改善这种免疫抑制状态;以8g/天的剂量使用NAC治疗安全性良好,希望为临床治疗进展期结直肠癌提供一条新途径。
Objective Through detecting some indexes such as CD3+TCR-ξbi-positive T-cell, IL-6,IL-10 and IFN-γ,of the patients with progressive colorectal carcinoma perioperatively,we had demonstrated that after operation,the organisms' immune state have aggravated further because of operation coup and other correlation factors, support the view of tumor-source immunosuppressive.These indexes changed after the operation because of the therapy for antioxidant N-acetylcysteine(NAC),the organisms' immune suppression state was amended,this is the emphasis of the experiment,so it confirm that after operation,the antioxidant NAC could amend the organisms' immune suppression state of the patients with progressive colorectal carcinoma.
Method The experiment choose 20 cases in which the patients suffered from colorectal carcinoma and have get radical surgery yet from TIANJIN Union Medicine Centre between October and December in 2006,in which 13 cases were males,7 females,ages from 31 to 77 years old,average 59.9 years.All of them had not accepted radiotherapy or chemical therapy,even any other medicine that can affect immune state.These 20 patients were divided into A and B group,10 cases each group,we took A as control group,and B as experiment group,the patients in B group had get NAC in vein dripping for 7 days after operations,8g everyday.The index including CD3+TCR-ξbi-positive T-cell,IL-6,IL-10 and IFN-γ,were detected both in A and B before operation,the 1st day,the 3rd day,the 7th day after operation respectively.By DIF through flow cytometry to detect CD3+TCR-ξbi-positive T-cell,and by ELISA to detect IL-6,IL-10 and IFN-γ.We use the statistics software SPSSl1.5 to analysis the data,and compare the difference of the index between pro-operation and after the operation,and between A and B group. If P＜0.05 it has statistical significance.
Result In control group IFN-γand CD3+TCR-ξbi-positive T-cell after operation were descended,but IL-10 was step up in most time subtotal distinction possess statistical significance,(P＜0.05).In experiment group CD3+TCR-ξbi-positive T-cell show augmented tendency than before operation,moreover difference in the 3rd and 7th day after operation have statistical significance,(P＜0.05).These changes contrast in control group:compared with IL-6 in most of time the index is lower than control group,distinction shows statistical significance.Although compared with after operation IFN-γdecreases like control group,but only in less time it had statistical significance:as the same the level of IL-10 does not have manifest upright tendency,only in the 3rd after operation show obvious difference, (P＜0.05).Compared experiment group and control group,in experiment group IFN-γand CD3+TCR-ξbi-positive T-cell are higher than in control group,and in most time it possess statistical significance,(P＜0.05);IL-6 and IL-10 after operation are lower than control group in most detecting time and the distinctions possess statistical significance.(P＜0.05.)
Conclusion It discovered that the organisms development immune suppression state in patients with progressive colorectal carcinoma after operation;the therapy of NAC could amend the organisms' immune suppression state;the dose of 8g/day was safety,and we expect that it could offer a new route for progressive colorectal carcinoma in clinical therapy.
引文
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