第 40 卷 8 期 2018 年 8 月宁夏医科大学学报 Journal of Ningxia Medical University 907 文章编号 : (2018) 论著腹腔镜与开腹胆囊切除术对胆囊良性病变患者肝脏和免疫功能影响的比较关旭, 赵仲明,

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1 第 40 卷 8 期 2018 年 8 月 Journal of Ningxia Medical University 907 文章编号 : (2018) 论著腹腔镜与开腹胆囊切除术对胆囊良性病变患者肝脏和免疫功能影响的比较关旭, 赵仲明, 祝进, 赵经川, 闫海燕, 牛孜耕 ( 宁夏银川市第二人民医院普通外科, 银川 ) 摘要 : 目的比较腹腔镜胆囊切除手术 (laparoscopy cholecystectomy,lc) 和开腹胆囊切除手术 (open cholecystectomy, OC) 对胆囊良性病变患者机体肝功能和免疫功能的影响方法 2013 年 1 月至 2015 年 12 月收治胆囊良性病变患者 80 例, 其中胆囊结石 25 例, 胆囊息肉 25 例, 慢性胆囊炎 30 例采用 LC 治疗的为 LC 组, 采用 OC 治疗的为 OC 组, 每组 40 例分析两组患者术前术后第 1 天及术后 1 周的肝功能及相关免疫指标的改变结果术后第 1 天两组的谷氨酸氨基转移酶 (ALT) 天冬氨酸氨基转移酶(AST) 和血清总胆红素 (TBIL) 均高于术前 (P 均 <0.05),LC 组 TBIL 低于 OC 组 (); 术后第 7 天,ALT 和 AST 均恢复到术前水平,TBIL 均仍高于术前 (), 但低于术后第 1 天 (P 均 <0.05), 且 LC 组低于 OC 组 (P 均 <0.05) 两组术后第 1 天与术前相比,CD3 + T 和 CD4 + T 均低于术前 (), 而 CD8 + T 高于术前 (); 两组术后第 7 天,3 项指标均恢复到术前水平, 术后第 7 天 CD3 + T CD4 + T CD8 + T 均高于术后第 1 天 (); 术后第 1 天的 IL-8 及 C 反应蛋白 (CRP) 较术前均升高 (P 均 <0.05),LC 组 IL-8 低于 OC 组 (), 术后第 7 天的 CRP 和 IL-8 比术前和术后第 1 天高 (P 均 <0.05) 且 LC 组 CRP 低于 OC 组 () 术后第 1 天 LC 组 IL-6 低于 OC 组 () LC 组患者的出血量和住院时间均低于 OC 组 (P 均 <0.01) 结论腹腔镜胆囊切除手术对胆囊良性病变患者的肝功能和免疫功能影响小关键词 : 胆囊良性病变 ; 腹腔镜 ; 开腹 ; 胆囊切除术 ; 免疫功能 ; 肝功能中图分类号 :R657.4 文献标识码 :A DOI: /j.cnki.issn 胆囊良性病变是目前较为常见的肝胆疾病, 临床表现为腹痛恶心呕吐, 伴随高热黄疸等, 若反复发作, 严重影响患者生活质量, 并可能诱 [1] 发胆道胰腺疾病, 威胁患者生命安全目前手 [2] 术仍然是胆囊病变的首选治疗方式, 而手术创伤对机体免疫系统具有抑制作用, 这也是术后感 [3] 染的重要原因随着外科技术的进步和外科设备的改进, 腹部手术逐渐向微创化方向发展, 腹腔镜手术应运而生其相对于开腹手术有手术创伤轻术后疼痛轻微恢复过程快住院时间较短以及术后美观等方面的优势但对患者肝脏和免疫功能的影响, 腹腔镜手术是否也同样具有优势, 尚未见相关报道本文比较腹腔镜胆囊切除术 (laparoscopic cholecystectomy,lc) 和开腹胆囊切除术 (open cholecystectomy,oc) 对胆囊良性病变患者的疗效, 并分析其对患者肝脏和免疫功能的影响收稿日期 : 基金项目 : 宁夏自然科学基金 (NZ15229) 作者简介 : 关旭, 副主任医师, 从事普外科的临床工作及研究 1 资料与方法 1.1 一般资料选取我院 2013 年 1 月至 2015 年 12 月收治的胆囊良性病变 ( 除外急性结石性胆囊炎患者 ) 需要手术患者 80 例, 分为两组, 各 40 例 OC 组男 21 例, 女 19 例, 年龄 22~75 岁, 平均 (52.9±13.2) 岁 ;LC 组男 27 例, 女 13 例, 年龄 24~75 岁, 平均 (50±11.2) 岁 80 例患者中胆囊结石 25 例, 胆囊息肉 25 例, 慢性胆囊炎 30 例纳入标准 :(1) 所有患者术前经过超声检查确诊为胆囊良性病变, 符合胆囊切除术手术指征 ;(2) 术前心肺肝肾等重要脏器功能无明显异常 ;(3) 无内分泌性疾病或自身免疫性疾病 ;(4) 所有患者均签署知情同意书排除标准 :(1) 患有心肺肝肾功能不全及病变内分泌系统血液系统自身免疫性疾病, 妊娠期或哺乳期妇女 ;(2) 术前肝脏功能明显异常者 ;(3) 围手术期输血手术过程中进行胆囊造影检查 ;(4)LC 术中转开腹者 ;(5) 对本研究不配合者两组患者一般资料比较差异无统计学意义 (P>0.05)

2 卷 1.2 手术方法 LC 组患者给予 LC 治疗, 行气管插管静吸复合麻醉, 采用四孔法或三孔法, 保持气腹压力在 12~15mmHg, 解剖 Calot 三角, 分离胆囊管及胆囊动脉, 分清胆总管和肝总管, 确认胆囊壶腹胆囊管以及胆囊动脉等并分别以生物夹结扎, 切除胆囊并使用电凝止血出血点 OC 组行 OC 治疗, 麻醉方法与观察组相同, 在右上腹腹直肌旁或右肋缘下缘做切口, 逐层切开进入腹腔, 分离胆囊至完整切除围手术期严格按照抗生素使用规范执行, 术前 30min, 术后最多 48h, 使用一代头孢菌素, 补充液体,LC 术后输液 2~4d,OC 术后输液 5~7d [4] 1.3 试剂及仪器人 CD3 + CD4 + 和 CD8 + T 细胞荧光抗体 ( 美国 ebioscience), 淋巴细胞分离液 ( 美国 ebioscience), Human IL -6 ELISA Kit 和 Human IL -8 ELISA Kit 试剂盒 ( 武汉博士德生物工程有限公司 ), 全自动电化学发光仪 ( 德国罗氏 E170), 流式细胞计数仪 (FACS Vantage 日本 ) 1.4 观察指标及检测方法采集两组患者术前及术后第 1 天和 7 天晨起空腹静脉血, 采用全自动电化学发光仪测定肝功能指标 : 谷氨酸氨基转移酶 (ALT) 天冬氨酸氨基转移酶 (AST) 血清总胆红素(TBIL); 使用流式细胞计数仪测定外周血 T 淋巴细胞及亚群水平 :CD3 + CD4 + 和 CD8 + T 细胞 ; 炎性指标 : 采用免疫比浊法测定 C 反应蛋白 (CRP); 利用 ELISA 法检测患者外周血中白细胞介素 6(IL-6) 和白细胞介素 8(IL-8) 的水平 1.5 统计学方法采用 SPSS 18.0 软件进行统计分析, 计量资料用均数 ± 标准差 (x±s) 表示, 同组内不同时间结果比较采用单因素方差分析 ; 同时间内两组间指标的比较采用两独立样本 t 检验,P 0.05 为差异有统计学意义 2 结果 2.1 胆囊良性病变患者 LC 和 OC 前后肝脏功能比较两组患者术后第 1 天的 ALT AST 和 TBIL 均高于术前 (P 均 <0.05),LC 组 TBIL 低于 OC 组 () 术后第 7 天,LC 组的 ALT 和 AST 均低于术前 (P 均 <0.05), 两组的 TBIL 均高于术前, 低于术后第 1 天 (P 均 <0.05); 且 LC 组 3 项指标均低于 OC 组 (P 均 <0.05), 见表胆囊良性病变患者 LC 和 OC 前后 T 细胞亚群比较术前两组之间的 3 种免疫细胞比较差异均无统计学意义 (P 均 >0.05); 与术前相比, 术后第 1 天两组的 CD3 + 和 CD4 + 均降低, 而 CD8 + 升高 (P 均 <0.05), 术后第 7 天与术后第 1 天比较,OC 组和 LC 组两组患者外周血中 CD3 + CD4 + 均升高, 而 CD8 + 均降低 (P 均 <0.05), 但两组比较差异均无统计学意义 (P 均 >0.05) 见图 1 表 1 胆囊良性病变患者 LC 和 OC 前后肝功能指标比较 (x±s) 时间组别 n ALT/(U L -1 ) AST/(U L -1 ) TBIL/( 滋 mol L -1 ) 术前 1 天 OC 组 ± ± ±3.13 LC 组 ± ± ±3.02 术后第 1 天 OC 组 ±2.53 * 28.44±3.08 * 26.34±2.05 * LC 组 ±2.22 * 27.26±2.25 * 23.38±1.89 *# 术后第 7 天 OC 组 ± ± ±2.09 * LC 组 ±1.12 * # 14.96±1.27 * # 12.36±1.51 * # 与同组术前 1 天比较 * ; 与同期 OC 组比较 # CD3 + T 细胞 /% CD4 + T 细胞 /% CD8 + T 细胞 /% 术前 1 天术后第 1 天术后第 7 天 OC 组 LC 组 OC 组 LC 组 OC 组 LC 组与同组术前 1 天比较 * 图 1 胆囊良性病变患者 LC 和 OC 前后 T 细胞亚群变化 (%)

8 期关旭, 等. 腹腔镜与开腹胆囊切除术对胆囊良性病变患者肝脏和免疫功能影响的比较 909 2.3 胆囊良性病变患者 LC 和 OC 前后炎性指标比较 3 种炎性指标 (CRP IL-6 和 IL-8) 两组术前比较差异均无统计学意义 (P 均 >0.05), 术后第 1 天较术前均增高 (P 均 <0.

3 8 期关旭, 等. 腹腔镜与开腹胆囊切除术对胆囊良性病变患者肝脏和免疫功能影响的比较胆囊良性病变患者 LC 和 OC 前后炎性指标比较 3 种炎性指标 (CRP IL-6 和 IL-8) 两组术前比较差异均无统计学意义 (P 均 >0.05), 术后第 1 天较术前均增高 (P 均 <0.05),LC 组 IL-8 低于 OC 组 (); 术后第 7 天的 CRP 和 IL-8 较术前和术后 1d 增高 (P 均 <0.05), 且 LC 组 CRP 低于 OC 组 (),IL-6 较术后第 1 天降低且 LC 组低于 OC 组 () 见图胆囊良性病变患者行 LC 和 OC 手术时间及术中出血量比较 LC 组患者术中出血量低于 OC 组 (P<0.01), 平均住院时间短于 OC 组 (P<0.01), 见表 2 CRP/(mg L -1 ) IL-6/(ng L -1 ) IL-8/(ng L -1 ) 术前 1 天术后第 1 天术后第 7 天 OC 组 LC 组 OC 组 LC 组 OC 组 LC 组与同组术前 1 天比较 * ; 与同期 OC 组比较 # 图 2 胆囊良性病变患者 LC 和 OC 前后炎性指标比较表 2 胆囊良性病变患者行 LC 和 OC 术中出血量及住院时间比较 (x±s) 组别 n 术中出血量 /ml 住院时间 /d OC 组 ± ±0.85 LC 组 ± ±0.61 t 值 P 值 <0.01 < 讨论手术创伤感染及外伤等任何刺激均会激发机体相应的应激反应系统, 促使机体发生全身性反应性炎症应答, 促进炎性细胞因子和相关激素的释放, 同时手术创伤引起内分泌及代谢方面发生复杂的变化, 甚至直接影响免疫系统或存在下丘脑 - 垂体 - 肾上腺轴和交感神经系统的变化, 在基因水平到细胞水平上, 影响机体的自身防御反应, 最终导致组织器官损伤甚至脓毒症, 延缓病 [5] 情恢复手术创伤促使包括单核 / 巨噬细胞和中性粒细胞等固有免疫细胞的活化, 使其产生大量的炎症介质, 导致机体免疫功能抑制, 机体对细菌感 [6-7] 染的概率极大增加虽然这些细胞理论上对机体有保护作用, 但是过度地释放会导致全身炎症反应综合征, 进而抑制机体的固有免疫反应侵 [8-9] 害细胞和组织乃至引起多器官功能障碍随着腹腔镜手术技术的发展和腹腔镜手术器械的不断完善, 腹腔镜手术应用在外科领域的范围更加广泛, 腹腔镜手术对机体正常生理内环境状态的影响, 主要表现在神经内分泌代谢免疫及循环等方面, 其中对机体应激反应的影响是病理生 [10] 理功能改变的基础国内外研究表明, 腹腔镜手术在细胞免疫体液免疫和非特异性免疫系统 [9-10] 等方面对机体抑制作用较开腹手术影响小, 对机体组织损伤程度轻, 机体的应激效应程度轻 [11] 微, 对人体生理功能干扰小腹腔镜手术对机体功能的影响, 是机体免疫应激代谢及循环等多因素多方面共同作用的体现目前关于腹腔镜手术的研究多集中于神经内分泌变化急性炎性细胞介质释放上因此, 本研究以胆囊良性病变者为实验对象, 从患者术后肝功能炎性反应及免疫功能方面比较 LC 和 OC 对于胆囊良性病变手术治疗的优劣, 以进一步深化认识腹腔镜手术对机体免疫功能的影响结果显示, 开腹手术在手术后对患者肝功能影响大, 引起的急性期炎症反应显著, 促使免疫细胞分泌大量炎性介质, 同时下调单核细胞表面活性分子, 从而影响单核细胞免疫功能, 使机体低表达炎性细胞因子, 机体固有免疫功能受损, 延缓术后病情恢复和增加了机体的感染率 ; 而腹腔镜手术一定程度上保留了单核细胞免疫功能, 有助于病原微生物的清除, 具有对患者肝功能影响小炎性反应轻和免疫细胞影响小的特点, 有利于病情恢复, 进而为进一步认识不同手术方式对机体的影响提供佐证参考文献 : [1] 殷俊杰, 蔡阳, 张筱凤, 等. 腹腔镜胆囊切除术并发胆管损伤患者的诊治 [J]. 中华肝胆外科杂志,2016,22 (1):27-29.

4 卷 [2] 刘承锋. 腹腔镜胆囊切除术后患者肝功能及免疫功能的变化 [J]. 腹腔镜外科杂志,2013,18(7): [3] Ng CSH,Lau KKW. Surgical trauma and immune functional chan -ges following major lung resection [J]. Indian J Surgery,2015,77(1): [4] 抗菌药物临床应用指导原则修订工作组. 抗菌药物临床应用指导原则 :2015 年版 [M]. 北京 : 人民卫生出版社,2015: [5] Gao X,Huang Y, Han Y,et al. The protective effects of Ambroxol in Pseudomonas aeruginosa-induced pneumonia in rats[j]. Archives of medical science: AMS,2011,7(3): [6] Lee SW,Feingold DL,Carter JJ,et al. Peritoneal macrophage and blood monocyte functions after open and laparoscopic -assisted cecectomy in rats [J]. Surgical Endoscopy And Other Interventional Techniques,2003,17(12): [7] Manson J,Thiemermann C,Brohi K. Trauma alarmins as activators of damage induced inflammation[j]. British Journal of Surgery,2012,99(S1): [8] Okapa R,Rak S,Wenda J,et al. Septic complications after multilocal fractures and multiple traumatic injury[j].chirurgia Narzadow Ruchu Iortopedia Polska, 2010,76(4): [9] Robertson CM,Coopersmith CM. The systemic inflammatory response syndrome[j]. Microbes and Infection,2006,8(5): [10] 王文杰, 王喜艳. 腹腔镜手术对机体应激和代谢反应的影响 [J]. 新疆医科大学学报,2009,32(9). [11] Haque Z,Rahman M,Siddique MA,et al. Metabolic and stress responses of the body to trauma: produced by the laparoscopic and open cholecystectomy[j]. Mymensingh Medical Journal,2004,13(1): ( 责任编辑 : 王秀玉 ) Effects of Laparoscopic Cholecystectomy and Open Cholecystectomy on Liver and Immune Function in Patients with Benign Gallbladder Disease GUAN Xu, ZHAO Zhongming, ZHU Jin, ZHAO Jingchuan, YAN Haiyan, NIU Zigeng (Department of General Surgery,Yinchuan Second People's Hospital,Yinchuan ) Abstract: Objective To compare the influence of liver function and immunologic function in patients with benign lesion of the gallbladder receiving laparoscopic cholecystectomy(lc)versus open cholecystectomy(oc). Methods From January 2013 to December 2015,80 cases of patients with benign lesion of the gallbladder including 25 cases of gallstone,25 cases of Gallbladder polyps,30 cases of chronic cholecystitis in our hospital were chosen and divided into LC group(40 cases) and OC group(40 cases). The LC group was treated with LC and the OC group was treated with OC. The liver function,immunologic function and inflammatory factor of the two groups were compared 1d before operation,1d and 7d after operation. Results The level of ALT,AST, TBIL were significantly increased 1d after operation when compared with those of pre-operation in two groups (). On day 7 after operation the level of ALT and AST recovered near to those of ld before operation, but TBIL levels were still higher than those of pre-operation(),less than those of 1d post-operation (). Furthermore,the three indexes in LC group were higher than those in OC group on the 7th day after operation. The levels of CD3 + and CD4 + 1d after operation were significantly decreased whereas the levels of CD8 + were significantly increased in two groups compared with those of pre-operation(). And the levels of CD4 + were obviously decreased in LC group compared with those in OC group, at the same time the levels of CD8 + were significantly elevated in OC group compared with those in LC group(). On the 7th day after operation the three index recovered to the levels of the pre-operation,but were still higher than those of 1d post-operation(). There were no differences between each group on 7th day after operation(p>0.05). The levels of IL-6,IL-8 and CRP were significantly increased on 1d after operation compared with those of ( 下转第 923 页 )

5 8 期郭莉, 等. 硫酸镁联合硝苯地平对子痫前期患者血清同型半胱氨酸胎盘生长因子及妊娠的影响 923 Analysis of the Effect of Magnesium Sulfate Combined with Nifedipine on Serum HCY,PLGF and Curative Effect on Pre-eclampsia GUO Li 1,2, TIAN Xiaojuan 2, YANG Zhiwei 1 (1. Ningxia Medical University, Yinchuan ; 2. Wuzhong People's Hospital Affiliated to Ningxia Medical University, Wuzhong ) Abstract: Objective To investigate the effect of magnesium sulfate combined with nifedipine on serum homocysteine(hcy),placental growth factor(plgf) and curative effect on pre-eclampsia. Methods Randomly selected 60 patients with pre-eclampsia, divided into observation group(n=30) treated with magnesium sulfate and nifedipine and control group(n=30) treated with magnesium sulfate. The expression of HCY and PLGF was detected by ELISA. Changes of blood pressure, proteinuria, liver and kidney function index, pregnancy outcomes,complications, and the birth of each group before and after treatment in patients were observed. Results The overall effective rate of the observation group(93.33%) was higher than that in the control group (66.67%)(). There was no significant difference between two groups before treatment(p>0.05). After treatment, HCY decreased(p<0.01) and PLGF increased(). There was no significant difference in HCY and PLGF between the two groups(p>0.05). After treatment, the mean arterial pressure,24h urine protein quantitation,bun,scr,alt,ast decreased(p<0.01). After treatment,the urinary protein quantitation, BUN and SCr of the observation group were lower than those of the control group( or <0.01). There were no significant differences in ALT and AST between the two groups(p>0.05). The incidence of adverse pregnancy outcomes in the observation group was 10.00%(3/30),which was lower than that in the control group 26.67%(8/30)(P=0.095),but the difference is not significant.the incidence of adverse outcomes in perinatal children was 16.67%(5/30),which was lower than the control group. The complication rate was 6.67%(2/30), which was lower than that of the control group(). Conclusion Magnesium sulfate and magnesium sulfate combined with nifedipine both can affect the expression of serum HCY and PLGF in patients with pre-eclampsia. But magnesium sulfate combined with nifedipine can significantly improve the clinical symptoms of patients with preeclampsia, reduce perinatal adverse outcomes and complications. Key words: pre-eclampsia;magnesium sulfate;nifedipine; homocysteine;placental growth factor ( 上接第 910 页 ) pre-operation() as well as the levels of IL-8 in OC group were higher than those in LC group(). The levels of IL-8 and CRP on the 7th day of post-operation were still significantly increased when compared with those of pre-operation and 1d post-operation(). Moreover the level of CRP in OC group was higher than that in LC group(). The level of IL-6 was obviously decreased when compared with that of 1d post-operation and less in LC group than that in OC group(). Amount of bleeding and hospital stays in LC group was obviously lower than OC group(). Conclusion LC has little influence on the liver and immunologic function of the patients,showing the advantage of minimal invasiveness with a safety and reliability. Therefore,it could be widely recommended in the clinic as a minimally invasive surgery. Key words: benign lesions of gallbladder; laparoscopy; laparotomy; cholecystectomy; immune function; liver function

211 better than those in the control group, with significant difference between two groups (P < 0.05). The ocular hypertension of patients in the cont

211 better than those in the control group, with significant difference between two groups (P < 0.05). The ocular hypertension of patients in the cont 210 毛果芸香碱联合拉坦前列素治疗原发性急性闭角型青光眼的疗效观察符元党 1, 郑振优 2, 林再雄 2, 周吉良 1. 昌江黎族自治县中西医结合医院, 海南昌江 572700 2. 海南医学院附属医院眼科, 海南海口 570100 1 摘要 : 目的探讨

第 40 卷 8 期 2018 年 8 月 宁夏医科大学学报 Journal of Ningxia Medical University 907 文章编号 : (2018) 论著 腹腔镜与开腹胆囊切除术对胆囊良性病变患者肝脏和免疫功能影响的比较 关旭, 赵仲明,

第 40 卷 8 期 2018 年 8 月宁夏医科大学学报 Journal of Ningxia Medical University 907 文章编号 : (2018) 论著腹腔镜与开腹胆囊切除术对胆囊良性病变患者肝脏和免疫功能影响的比较关旭, 赵仲明,