【作者】 李梅；

【导师】 崔晓楠；

【作者基本信息】 大连医科大学 ， 中西医结合临床， 2017， 硕士

【摘要】 背景与目的结直肠癌是世界上常见的恶性肿瘤之一,手术是目前结直肠癌主要的根治性手段,手术创伤引发的炎症是导致患者胃肠道功能紊乱至关重要的因素,对患者生存质量、机体功能恢复、肿瘤术后辅助治疗及预后转归具有重要影响。以改善术后炎症及相关并发症为代表的快速康复理念新近成为现代外科研究的热点,但由于操作繁琐、费用较高限制了其临床应用。研究表明,以电针为代表的中医治疗方法能够改善患者术后炎症,提高机体免疫,是富有前景的术后快速恢复治疗手段,然而机制尚不明确。本实验对60例结直肠癌术后患者进行了电针联合常规治疗与常规治疗的随机独立对照实验研究,观察患者术后首次排气、首次排便恢复时间及外周血中白细胞、中性粒细胞、淋巴细胞数目变化,检测炎症免疫相关细胞因子IL-2、IL-6、IL-8水平,为电针治疗结直肠癌术后胃肠功能快速恢复提供理论依据。材料与方法1.本研究选取大连医科大学第一附属医院肛肠外科2016年9月-2017年2月符合纳入标准的60例接受结直肠癌手术治疗的患者。其中:男性48例,女性22例;年龄41-80岁,中位年龄64岁。把患者分为实验组和对照组,每组各30例。对照组术后进行常规治疗,实验组在常规治疗基础上从术后24h开始进行电针治疗,每天一次,每次30分钟,连续五天。观察记录患者术后首次排气、首次排便恢复时间。2.分别采集患者手术前、术后24小时（针灸治疗前）及第6天（针灸治疗后）外周血。使用酶联免疫吸附法（ELISA）,用酶标仪测量各孔在450nm的吸光度（OD）值,依据所测OD值及所配标准品的浓度算出标准曲线的直线回归方程,计算出各待测样品的IL-2、IL-6及IL-8的表达量。通过临床患者血液常规检测报告分析白细胞、中性粒及淋巴细胞数量的变化。3.本实验中所有数据均使用SPSS 20.0统计软件进行数据统计分析。用卡方检验来分析计数资料,用T检验来分析计量数据,不同时间重复测量数据采用重复测量设计资料的方差分析,用平均数±标准差来表示计量资料。结果1.患者一般资料分析两组患者在性别（P=0.592>0.05）、年龄（P=0.371>0.05）、肿瘤位置（P=0.292>0.05）、肿瘤分期（P=0.362>0.05）、手术时长（P=0.273>0.05）比较,均无统计学差异,组间均衡,具有可比性。2.首次排气、排便情况（1）首次排气时间实验组患者术毕至首次出现排气时间（58.58±18.61h）显著短于对照组（73.93±28.34h）,P=0.017<0.05。（2）首次排便时间实验组患者术毕至首次出现排便时间（110.57±33.48h）显著短于对照组（135.56±37.81h）,P=0.013<0.05。3.外周血中白细胞、中性粒细胞及淋巴细胞变化情况（1）白细胞变化情况实验组和对照组患者白细胞术后24小时及术后第6天不同时间点均有显著变化(F_时点=148.072,P_时点=0.000<0.05);两组白细胞随时间变化趋势程度不同,实验组和对照组白细胞均先升高再降低,但在术后24小时以后实验组降低程度更大,差异具有统计学意义(F_交互=4.9,P_交互=0.013<0.05)。（2）中性粒细胞变化情况实验组和对照组患者中性粒细胞术后24小时及术后第6天不同时间点均有显著变化(F_时点=142.874,P_时点=0.000<0.05);两组中性粒细胞随时间变化趋势程度不同,实验组和对照组中性粒细胞均先升高再降低,但在术后24小时以后实验组降低程度更大,差异有统计学意义(F_交互=3.392,P_交互=0.037<0.05)。（3）淋巴细胞变化情况:实验组和对照组患者淋巴细胞术后24小时及术后第6天不同时间点均有显著变化(F_时点=78.63,P_时点=0.000<0.05);实验组和对照组淋巴细胞均先降低再升高,并且术后24小时两组患者淋巴细胞差异较大,可能是手术对淋巴细胞影响存在个体差异,需进一步扩大样本量分析电针对术后淋巴细胞的影响。4.血清IL-2、IL-6及IL-8检测结果（1）血清IL-2变化情况实验组和对照组患者血清IL-2术后24小时及术后第6天不同时间点均有显著变化(F_时点=28.494,P_时点=0.000<0.05);两组血清IL-2随时间变化趋势程度不同,实验组和对照组血清IL-2均先降低再升高,但在术后24小时以后实验组升高程度更大,差异有统计学意义(F_交互=6.181,P_交互=0.010<0.05)（2）血清IL-6变化情况实验组和对照组患者血清IL-6术后24小时及术后第6天不同时间点均有显著变化(F_时点=49.887,P_时点=0.000<0.05);两组血清IL-6随时间变化趋势程度不同,实验组和对照组血清IL-6均先升高再降低,但在术后24小时以后实验组降低程度更大,差异有统计学意义(F_交互=3.694,P_交互=0.032<0.05)（3）血清IL-8变化情况实验组和对照组患者血清IL-8术后24小时及术后第6天不同时间点均有显著变化(F_时点=28.106,P_时点=0.000<0.05);两组血清IL-8随时间变化趋势程度不同,实验组和对照组血清IL-8均先升高再降低,但在术后24小时以后实验组降低程度更大,差异有统计学意义(F_交互=3.625,P_交互=0.049<0.05).结论1.电针治疗改善结直肠癌术后首次排气、排便。2.电针促进胃肠功能恢复可能与促进外周血中白细胞、中性粒细胞恢复正常及调节炎症免疫相关细胞因子IL-2、IL-6和IL-8的表达相关。更多还原

【Abstract】 Background and aimsColorectal cancer is one of the most common malignant tumors in the world.Surgical treatment is the only radical cure in colorectal cancer.However,inflammation caused by surgical trauma is a vital factor in gastrointestinal dysfunction,which influences the quality life and the recovery of body function,postoperative adjuvant therapy and prognosis.It’s a hot spot to prove FTS（fast track surgery）which represented by postoperative inflammation and related complications.But the clinical application of FTS has been limited due to the high cost and complexity of the operation.The study shows that the method of external treatment of Chinese medicine,which is represented by electroacupuncture（EA）,can alleviate the postoperative inflammatory condition and boost the immune system.It is a promising treatment of rapid recovery after operation,but the mechanism is not clear and needs further study.In this study,independent random control research that compared 60 colorectal cancer patients treated with EA and routine treatment with routine treatment alone was conducted.After surgery,the recovery time of the first exhaust and the first defecation after operation were recorded.At the same time,the inflammatory related cytokines IL-2,IL-6,IL-8 and white blood cells,neutrophils,lymphocytes that are closely connected with the inflammatory were detected.The objective is to explore the mechanism by which EA promote the recovery of gastrointestinal functions and provide important basis of the experimental data.Materials and methods:1.A total of 60 patients who underwent resection of colorectal cancer and accorded with the inclusive criteria at the anorectal department of the first affiliated hospital of dalian medical university from September,2016 to February,2017 were selected in this research.In these cases,48 patients are male,22 patients are female.The ages of patients are from 41 to 80,and the mean age is 64.Those patients were divided into EA treatment group and control group with conventional treatment 30cases respectively.After resection of colorectal cancer,the control group patients were treated with conventional treatment while patients in EA treatment group received conventional treatment and EA treatment from the 24 hours after operation,once a day,30min one time,in all five days.We recorded the recovery time of the first exhaust and the first defecation after operation.2.We respectively collected blood of patients before surgery,at the 24 hours after surgery and at the 6th day after surgery.We detected absorbance（OD）values of the wells at 450nm by enzyme-linked immunosorbent assay（ELISA）using a microplate reader.Then we calculated the standard curve of the linear regression equation according to the OD value and the concentration of the standard.The changes in the number of white blood cells,neutrophils and lymphocytes were analyzed by routine blood tests.3.All the data in this experiment were analyzed by SPSS 20.0 statistical software.The chi-square test was used to analyze the count data and the mean±standard deviation was used to denote the measurement data.We detected data that were consistent with the normal distribution and variance homogeneity test by analysis of variance,and we analyzed repeated-measurement data by time point interaction.Results1.General analysis of patientsThe gender（P=0.592>0.05）,age（P=0.371>0.05）,tumor location（P=0.292>0.05）,tumor stage（P=0.362>0.05）,surgery time（P=0.273>0.05）of the two groups were not statistically significant and achieved the object of data acquisition.2.The first exhaust and defecation situation after operation（1）The first exhaustCompared with control group（73.93±28.34 h）,the first time（58.58±18.61 h）of exhaust after operation was significantly shorter（P=0.017<0.05）.（2）The first defecationCompared with control group（135.56±37.81 h）,the first time（110.57±33.48h）of defecation after operation was significantly shorter（P=0.013<0.05）.3.Changes of white blood cells,Neutrophils and Lymphocytes in Peripheral Blood（1）Changes of white blood cellsCompared with preoperative,the numbers of WBCs in the two groups were both significantly changed at 24 hours and 6 days after operation(F_time=148.072,P_time=0.000<0.05).The change trend levels were different in two groups.The WBCs first increase and then decrease in both two groups,but test group decreased more notable than that of the control group from 24 hours after operation.The difference between the two groups was statistically significant(F_interacion=4.9,P _interacion=0.013<0.05).（2）Changes of neutrophilsCompared with preoperative,the numbers of neutrophils in the two groups were both significantly changed at 24 hours and 6 days after operation(F_time=142.874,P_time=0.000<0.05).The change trend levels were different in two groups.The neutrophils first increase and then decrease in both two groups,but test group decreased more notable than that of the control group from 24 hours after operation.The difference between the two groups was statistically significant(F_interacion=3.392,P _interacion=0.037<0.05).（3）Changes of lymphocytesCompared with preoperative,the numbers of lymphocytes in the two groups were both significantly changed at 24 hours and 6 days after operation(F_time=78.63,P_time=0.000<0.05).The lymphocytes first decrease and then increase in both two groups,and there was a significantly difference between the two groups at 24 hours after operation.This may due to the different effect on different patients by operation.We need continually increase sample sizes to study the effect of EA on lymphocytes.4.IL-2,IL-6 and IL-8 test results in serum（1）Serum IL-2 levelsCompared with preoperative,the levels of IL-2 in the two groups were both significantly changed at 24 hours and 6 days after operation(F_time=28.494,P_time=0.000<0.05).The change trend levels were different in two groups.The IL-2 first decrease and then increase in both two groups,but test group increased more notable than that of the control group from 24 hours after operation.The difference between the two groups was statistically significant(F_interacion=6.181,P _interacion=0.010<0.05).（2）Serum IL-6 levelsCompared with preoperative,the levels of IL-6 in the two groups were both significantly changed at 24 hours and 6 days after operation(F_time=49.887,P_time=0.000<0.05).The change trend levels were different in two groups.The IL-6 first increase and then decrease in both two groups,but test group decreased more notable than that of the control group from 24 hours after operation.The difference between the two groups was statistically significant(F_interacion=3.694,P _interacion=0.032<0.05).（3）Serum IL-8 levelsCompared with preoperative,the levels of IL-8 in the two groups were both significantly changed at 24 hours and 6 days after operation(F_time=28.106,P_time=0.000<0.05).The change trend levels were different in two groups.The IL-8 first increase and then decrease in both two groups,but test group decreased more notable than that of the control group from 24 hours after operation.The difference between the two groups was statistically significant(F_interacion=3.625,P _interacion=0.049<0.05)Conclusion1.EA treatment can promote the recovery of the first exhaust and defecation after colorectal cancer operation.2.The promotion of gastrointestinal function by EA treatment maybe associated with the regulation of white blood cells and Neutrophils,the overexpression of cytokines IL-2 and the inhibition of IL-6 and IL-8,which can improve postoperative inflammation.更多还原