Effects of general anesthesia combined with epidural anesthesia on brain gut peptide, intestinal barrier function and oxidative stress in patients with colorectal cancer
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摘要: 目的 分析全身麻醉联合硬膜外麻醉对结直肠癌患者脑肠肽、肠屏障功能及氧化应激反应的影响。 方法 选择本院行根治性手术的86例结直肠癌患者为研究对象,均经病理学检查确诊为结直肠癌。采用随机数字表法将患者分为2组,其中将采用单纯全身麻醉的43例患者纳入对照组,全身麻醉联合硬膜外麻醉的43例患者纳入观察组。对比2组患者脑肠肽、肠屏障功能及氧化应激反应指标。 结果 术前, 2组患者胃动素、胃泌素及饥饿素比较差异无统计学意义(P>0.05)。术后,观察组胃动素及饥饿素水平均显著高于对照组(P<0.05), 但2组胃泌素对比差异无统计学意义(P>0.05)。术前, 2组患者血清二胺氧化酶、D-乳酸及内毒素对比差异无统计学意义(P>0.05); 治疗后, 2组患者以上指标水平均显著下降,但对照组下降幅度更大(P<0.05)。治疗后, 2组患者超氧化物歧化酶(SOD)、谷胱甘肽(GSH)均显著升高,但对照组升高幅度更大(P<0.05); 治疗后, 2组患者血清丙二醛(MDA)水平均呈显著下降趋势,但对照组下降更显著(P<0.05)。 结论 与单纯全身麻醉相比,全身麻醉联合硬膜外麻醉可减少对结直肠癌患者脑肠肽、肠屏障功能及氧化应激反应的影响。Abstract: Objective To analyze the effects of general anesthesia combined with epidural anesthesia on brain-gut peptide, intestinal barrier function and oxidative stress in patients with colorectal cancer. Methods Eighty-six patients with colorectal cancer who undergoing radical surgery in our hospital were enrolled as study objects, and were confirmed as colorectal cancer by pathological examination. Patients were divided into two groups by random number table method, among whom 43 cases with general anesthesia were selected as control group, and another 43 patients combining general anesthesia and epidural anesthesia were selected as observation group. The brain intestinal peptide, intestinal barrier function and oxidative stress response index were compared between the two groups. Results There were no significant differences in motilin, gastrin and ghrelin between the two groups before operation(P>0.05). The levels of motilin and ghrelin after operation in the observation group were significantly higher than those in the control group(P<0.05), but no significant difference in gastrin was observed between the two groups(P>0.05). There were no significant differences in serum diamine oxidase, D-lactate and endotoxin between the two groups before operation(P>0.05). After treatment, the above indicators in the two groups decreased significantly, but the control group decreased more significantly(P<0.05). After treatment, the superoxide dismutase - (SOD), glutathione(GSH)of the two groups were significantly increased, but the control group increased more significantly(P<0.05). After treatment, the serum malondialdehyde(MDA)level of the two groups showed a significant decrease trend, but the control group decreased more significantly(P<0.05). Conclusion Compared with general anesthesia alone, general anesthesia combined with epidural anesthesia can reduce the effects on brain gut peptide, intestinal barrier function and oxidative stress in colorectal cancer patients.
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放射治疗是复发性鼻咽癌治疗的重要手段之一,约60%以上的复发性鼻咽癌采用放射治疗后能提高临床疗效及生存率[1]。尽管放射治疗设备有所更新,放射治疗技术如调强放疗、适行放疗等取得了进步,但仍需避免或减少放疗不良反应的发生[2-4]。本研究选取99例均为确诊复发性鼻咽癌放疗的患者为研究对象,探讨中医辨证治疗对血液、放射性皮肤损伤和放疗后症候反应的影响,现报告如下。
1. 资料与方法
1.1 一般资料
选取2007年5月—2013年4月南部战区总医院收治的99例复发性鼻咽癌患者为研究对象,采用随机数字表法分为观察组(52例)和对照组(47例)。观察组女24例,男28例; 年龄31~69岁,平均(48.32±6.22)岁; 肺热壅盛型16例,气阴两虚型19例,痰凝血瘀型17例。对照女21例,男26例; 年龄32~65岁,平均(47.12±5.96)岁; 肺热壅盛型15例,气阴两虚型17例,痰凝血瘀型15例。2组基本资料(年龄、性别、中医辨证分型)比较,差异无统计学意义(P>0.05)。纳入标准: 全部患者均经PET/CT或头颈部MRI确诊,存在可测量的肿瘤复发病灶; 患者预计生存期>6个月。排除标准: 合并神经系统疾病,肝、肾功能不全者; 有其他肿瘤手术史、放化疗史者; 哺乳期、妊娠期妇女。本研究经医学伦理委员会评审通过,患者知情并自愿签署知情同意书。
1.2 方法
观察组实施放射治疗。以高能X线三野照射(1.8~2 Gy/F, 5 F/W)在模拟机下定位,范围为原发病灶及区域淋巴结引流区的照射总量为40~60 Gy。校正放射野2周1次。中医辨证用药: 肺热壅盛型患者采用清热泻肺汤加减,其中组方包括百部12 g, 桑白皮15 g, 胆南星6 g, 黄芩12 g, 蝉蜕12 g, 苍术9 g, 连翘12 g, 辛夷花12 g, 苍耳子12 g, 桔梗12 g, 细辛3 g, 北杏仁15 g, 白芷12 g, 蒲公英12 g, 随症加减; 气阴两虚型患者采用生脉散合增液汤加减,组方包括人参9 g, 生地15 g, 麦冬30 g, 菖蒲6 g, 玄参30 g, 远志12 g, 赤芍12 g, 随症加减; 痰凝血瘀型患者采用柴胡疏肝散合通窍活血加减,组方包括柴胡12 g, 半夏12 g, 郁金12 g, 白芍12 g, 青皮12 g, 皂角刺12 g, 丹参12 g, 枳壳12 g, 川芎9 g, 大枣12 g, 茯苓18 g, 桃仁12 g, 牡蛎18 g, 海藻18 g, 浙贝母18 g, 随症加减。对照组放疗方法同观察组。
1.3 观察指标
1.3.1 骨髓抑制
分别于放疗前1 d、放疗结束后4周检测血红蛋白(Hb)、白细胞计数(WBC)、血小板(PLT)。骨髓抑制分级标准采用世界卫生组织(WHO)毒副作用分级标准[5]进行评定, 分为0~Ⅳ度。
1.3.2 放射性皮肤损伤程度
根据皮肤放射损伤评分标准量表(RTOG)[6]对放射性皮肤损伤程度进行评价。0度为皮肤无变化; 1度为出现轻度皮肤红斑、干性脱发、滤泡,出汗减少,患者生活质量不受影响,痛苦小; 2度为出现明显皮肤红斑、湿性斑状皮炎和中度水肿; 3度为出现融合性湿性皮炎和凹陷性水肿; 4度为皮肤坏死,合并溃疡出血,甚至被迫终止放疗。
1.3.3 症候指标
口腔黏膜炎、胃肠道反应、口干症、张口受限等。
1.4 统计学方法
采用SPSS 23.0软件进行统计分析,计量资料行t检验,以(x±s)表示,计数资料行χ2检验,以[n(%)]表示, P < 0.05表示差异有统计学意义。
2. 结果
2.1 2组血液检测指标水平比较
观察组治疗前后血液检测指标水平比较,差异无统计学意义(P>0.05)。对照组治疗前后血液检测指标水平比较,差异有统计学意义(P < 0.05)。观察组血液检测指标水平高于对照组,差异有统计学意义(P < 0.05或P < 0.01), 见表 1。
表 1 2组血液检测指标水平比较(x±s)组别 n 时点 Hb/(g/L) WBC/(×109/L) PLT/(×109/L) 观察组 52 治疗前 137.60±23.24 4.74±0.94 216.90±31.80 治疗后 132.58±20.13# 4.44±1.24# 210.73±29.21# 对照组 47 治疗前 132.67±29.36 4.77±1.09 217.46±35.84 治疗后 122.56±28.24* 3.59±1.00* 180.37±25.69* Hb: 血红蛋白; WBC: 白细胞计数; PLT: 血小板。与治疗前比较, *P < 0.05; 与对照组比较, #P < 0.05。 2.2 2组放射性皮肤损伤比较
观察组1度皮肤损伤16例, 2度皮肤损伤18例, 3度皮肤损伤15例, 4度皮肤损伤3例; 对照组1度皮肤损伤5例, 2度皮肤损伤19例, 3度皮肤损伤17例, 4度皮肤损伤6例。观察组皮肤损伤患者占比与对照组比较,差异有统计学意义(P < 0.05)。观察组平均治愈时间(7.78±2.32) d, 对照组为(13.73±3.16) d。观察组皮肤损伤平均治愈时间短于对照组,差异有统计学意义(P < 0.05)。
2.3 2组放疗后症候发生情况比较
放疗后,观察组口腔黏膜炎、胃肠道反应、口干症、张口受限发生率低于对照组,差异有统计学意义(P < 0.05)。见表 2。
表 2 2组放疗后症候反应发生情况比较[n(%)]组别 n 口腔黏膜炎 胃肠道反应 口干症 张口受限 观察组 52 30(57.7)* 31(59.6)* 27(51.9)* 33(63.5)* 对照组 47 37(78.7) 38(80.9) 42(89.4) 39(83.0) 与对照组比较, *P < 0.05。 3. 讨论
鼻咽癌是中国南部各地区头颈部较常见的恶性肿瘤,放射治疗是鼻咽癌的主要治疗手段之一[7]。复发性鼻咽癌患者需加大放射剂量才能提高疗效,随着常规照射剂量的增加,患者皮肤、颞颌关节、腮腺、脊髓等组织会出现损伤,并会表现出骨髓抑制、放射性皮炎、张口受限、黏膜反应、口干症、消化道反应等毒副作用,从而降低患者对放疗的耐受性和依从性,甚至延长放疗疗程或导致治疗终止[8]。
鼻咽癌在中医学中属于“失荣”“上石疽”“鼻渊”等范畴,中医学认为,放射线属于火热之毒邪,作用于人体后可引起经脉痹阻、阴液亏虚,肌肤筋骨失去濡养,表现为吞咽困难、口干咽燥、张口受限、皮肤损伤等。此外,肿瘤患者均有一定程度的正气虚损,接受放疗时,火热毒邪攻伐机体,导致体内热毒之邪积聚,邪气过剩,耗气伤阴。“精气夺则体更虚”,加之癌毒附着,脾胃之功能受损加剧,气血生化不足,造成气阴两虚、气血损伤,临床表现为纳差、恶心、呕吐等胃肠道反应,也可能出现贫血、血小板减少、白细胞下降等骨髓抑制表现[9]。中医辨证论治过程中对患者治疗期间出现的有关症候、系统整体状态和功能溯本求源,发现鼻咽癌患者以肺热壅盛、痰凝血瘀和气阴两虚3种证型为主,因此基本治疗原则应以清泻肺热、化痰活血、益气养阴为主[10]。
中医辨证治疗能够提高鼻咽癌患者的机体免疫功能,减轻放疗毒性反应。研究[11]发现,黄芪注射液能够减轻肿瘤放化疗的毒副作用,保护骨髓,防止白细胞下降。林冯杰等[12]研究显示,参麦注射液能显著减轻晚期鼻咽癌患者放射性皮肤损伤。本研究结果显示,观察组血液检测指标水平高于对照组,差异有统计学意义(P < 0.05或P < 0.01); 观察组皮肤损伤平均治愈时间短于对照组,差异有统计学意义(P < 0.05); 观察组口腔黏膜炎、胃肠道反应、口干症、张口受限发生率低于对照组,差异有统计学意义(P < 0.05)。以上结果提示,中医辨证治疗能够在复发性鼻咽癌放疗过程中起到减毒作用。但目前对中医药放疗的减毒机制尚不明确,研究应从细胞分子生物学机制上继续深入探讨,同时还需设计更先进的试验方法以观察中医药对放疗减毒作用的影响。
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