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围手术期针刺对手术应激反应的影响
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摘要
目的:
     1.初步观察围手术期针刺对术后机体心肺、胃肠等各项功能恢复及术后镇痛的影响。
     2.从应激反应各个方面,包括炎症应激、氧化应激、心理应激等初步研究围手术期针刺对手术应激反应的影响。
     3.在动物实验基础上,初步探讨围手术期针刺对手术应激反应影响的机理,为临床应用提供一定的理论基础。
     方法:
     临床研究
     1.分组:将符合纳入标准的60例拟行妇科腹腔镜手术患者随机分为2组:对照组与针刺组,每组30例。
     2.治疗:对照组只予以术后妇科病房常规基础治疗;针刺组:除予以术后妇科病房常规基础治疗外,加用针刺。针刺方法:采用导师张宏教授的针刺调神方。选穴:四神聪、神庭、印堂、内关(双侧)、三阴交(双侧)。操作:四神聪、神庭、印堂、内关(双侧)、三阴交(双侧)用1寸毫针(0.35×25)刺入,神庭、四神聪、印堂行捻转手法,平补平泻,内关、三阴交行提插兼捻转手法,平补平泻。行手法后留针(针刺深度约0.5-0.8寸),治疗30分钟后出针。疗程:术前1小时、术后2小时及术后第1-3天每天治疗一次,共5次。
     3.观察指标:(1)围手术期针刺对机体整体机能的影响:①术后镇痛作用;②对术后心肺功能的调整作用;③对术后胃肠功能的调整作用;④对术后不良反应及并发症发生情况的影响。(2)围手术期针刺对术后机体应激反应的影响,观测血浆促肾上腺皮质激素(ACTH)和皮质醇(Cot)浓度的变化;(3)围手术期针刺对术后机体急性炎症应激的影响,观测血清白细胞介素IL-6与IL-10浓度的变化;(4)围手术期针刺对术后机体氧化应激的影响,观测血浆丙二醛(MDA)和一氧化氮(NO)浓度的变化;(5)围手术期针刺对手术前后机体心理应激的影响,观察焦虑自评量表(SAS)和抑郁自评量表(SDS)评分的变化。
     实验研究
     1.分组:30只雄性清洁级SD大鼠,随机分为空白组(阴性对照组)、手术组(阳性对照组)、和手术加针刺组(实验组),每组10只,共30只。
     2.步骤:(1)建立部分肝切除大鼠模型;(2)针刺方法:取头部“四神聪”、“神庭”、“印堂”,用0.30×13mm针灸针平刺5mm,取双侧“内关”、“三阴交”用0.30×13mm针灸针直刺5mm,捻转后,同侧“内关”、“三阴交”接G6805型电针仪给予“疏密波”,强度以引起大鼠肢体肌肉轻微抖动而不嘶叫为宜(强度1-2mA)。治疗30分钟后出针。手术加针刺组大鼠在手术前1小时、术后2小时,均给予针刺,共针刺2次。(3)取材及标本制作:于大鼠部分肝切除术后应激反应最显著时间即术后12小时,三组大鼠同时处死取材:包括肝脏、海马、下丘脑组织分别制作标本或超低温冻存。
     3.观察指标:(1)肝脏HE染色常规病理片观察;(2)肝脏GR蛋白表达分析,采用免疫组织化学法;(3)海马GR mRNA表达分析,采用逆转录PCR法(RT-PCR);(4)下丘脑CRH mRNA表达分析,采用逆转录PCR法(RT-PCR)。
     结果:
     临床研究
     1.围手术期针刺对机体整体机能的影响
     (1)围手术期针刺的术后镇痛作用
     在VAS评分中,两组术后6小时评分最高,明显高于本组术后第1天与术后第3天(P<0.05),而且在术后第1天与术后第3天两个时点上,针刺组评分明显低于对照组(P<0.05)。在BCS评分中,得分变化趋势与VAS相反,两组术后6小时评分最低,明显低于本组术后第1天、术后第3天(P<0.05),而且在术后第1天与术后第3天两个时点上,针刺组评分明显高于对照组(P<0.05)。
     (2)围手术期针刺对术后心肺功能的调整作用
     两组术前心肺功能各项指标无明显差异。在收缩压(SBP)观察中,两组术毕回房后均较术前有所升高(P<0.05),至术后第1天两组SBP均降至术前水平。在舒张压(DBP)观察中,对照组术毕回房后较术前有所升高(P<0.05),而针刺组术毕回房后与术前相比无明显变化,至术后第1天对照组DBP降至术前水平。在心率(HR)观察中,对照组术毕回房后较术前明显加快(P<0.05),而针刺组术毕回房后较术前无明显变化(P>0.05),至术后第1天对照组HR恢复至术前水平,而且术毕回房后,针刺组心率明显低于对照组(P<0.05)。在血氧饱和度(SPO:)、呼吸(RR)观察中,两组术前、术毕回房后、术后第1天3个时点组内两两比较及组间比较均无明显差异(P>0.05)。
     (3)围手术期针刺对术后胃肠功能的调整作用
     针刺组术后肛门排气、排便时间明显短于对照组,差异有统计学意义(P<0.05)。
     (4)围手术期针刺对术后不良反应及并发症发生情况的影响
     观察期间,两组均未出现并发症。在几种主要不良反应中,针刺组与对照组比较差异无统计学意义,但在恶心呕吐、腹胀两方面,针刺组发生率有相对较低的趋势,分析原因可能为本研究样本量较小,如以后有机会开展大样本量研究,可能会显现出针刺在这方面的优势。
     2.围手术期针刺对术后机体应激反应的影响
     两组患者术前血浆ACTH、Cor浓度无明显差异,术后ACTH、Cor浓度均明显升高,术后6小时浓度最高,随后逐渐下降,两组术后6小时、术后第1天均明显高于术前(P<0.05),至术后第3天针刺组降至术前水平,对照组仍高于术前水平(P<0.05)。术后6小时与术后第1天,针刺组ACTH、Cor浓度明显低于对照组(P<0.05)。
     3.围手术期针刺对术后机体急性炎症应激的影响
     两组患者术前血清IL-6浓度均无明显差异,术后IL-6浓度明显升高,术后6小时浓度最高,随后逐渐下降,两组术后6小时、术后第1天与术后第3天均明显高于术前(P<0.05);术后6小时、术后第1天与术后第3天,针刺组IL-6浓度明显低于对照组(P<0.05)。两组患者术前血清IL-10浓度无明显差异,术后IL-10浓度明显升高,术后6小时浓度最高,随后逐渐下降,两组术后6小时、术后第1天均明显高于术前(P<0.05),至术后第3天针刺组降至术前水平,对照组仍高于术前水平(P<0.05);术后6小时与术后第1天,针刺组IL-10浓度明显低于对照组(P<0.05)
     4.围手术期针刺对术后机体氧化应激的影响
     两组患者术前血浆MDA浓度均无明显差异,术后MDA浓度明显升高,术后6小时浓度最高,随后逐渐下降,两组术后6小时、术后第1天均明显高于术前(P<0.05);虽然两组整体比较差异无统计学意义,但在术后6小时、术后第1天,针刺组MDA浓度明显低于对照组(P<0.05)。两组患者术前血浆NO浓度均无明显差异,术后NO浓度明显降低,术后6小时浓度最高,随后逐渐上升,两组术后6小时、术后第1天与术后第3天均明显低于术前(P<0.05);术后6小时、术后第1天,针刺组NO浓度明显高于对照组(P<0.05)。
     5.围手术期针刺对手术前后机体心理应激的影响
     两组术前SAS、SDS评分无明显差异;虽然术后第7天两组SAS、SDS评分均明显低于术前(P<0.05),但针刺组术后第7天SAS、SDS评分明显低于对照组(P<0.05)。
     实验研究
     1.肝脏HE染色常规病理片观察
     空白组:镜下为基本正常肝组织;手术组:镜下均可见轻重不等的肝细胞水肿改变;部分重度肝细胞水肿,范围广泛,细胞气球样变,肝小叶结构不清,仅见少量正常肝细胞;部分伴有肝细胞脂肪变性,在肝细胞内可见小脂肪空泡。手术加针刺组:大部分镜下为基本正常肝组织,小部分为轻度肝细胞水肿,主要分布在肝小叶周边区域。
     2.肝脏GR蛋白表达分析(免疫组化法)
     空白组肝脏组织中GR广泛表达。手术组与空白组相比细胞浆和细胞核中GR的阳性染色均显著减弱,差异有统计学意义(P<0.05);手术加针刺组肝细胞中GR的阳性染色虽然也有部分减弱,但与空白组相比差异无统计学意义(P<0.05)。
     3.海马GR mRNA表达分析(RT-PCR)
     术后手术组与手术加针刺组海马GR mRNA表达与空白组相比均有不同程度降低,差异有统计学意义(P<0.05),但与手术组相比,手术加针刺组海马GR mRNA表达相对较高,差异有统计学意义(P<0.05)。
     4.下丘脑CRH mRNA表达分析(RT-PCR)
     术后手术组与手术加针刺组下丘脑CRH mRNA表达与空白组相比均有不同程度升高,差异有统计学意义(P<0.05),但与手术组相比,手术加针刺组下丘脑CRH mRNA表达相对较低,差异有统计学意义(P<0.05)。
     结论:
     1.围手术期应用针刺调神方可明显缓解术后疼痛,这提高了患者的术后舒适程度;并且有利于稳定血压和心率,使术后循环功能保持平稳;还能够促进术后胃肠功能尽快恢复,有利于减少术后术后胃瘫综合征及肠麻痹的发生。
     2.围手术期应用针刺调神方能够调控术后血浆ACTH、Cor水平,从而在一定程度上调整了术后机体应激反应,这有利于防治术后过度应激对机体造成损害。
     3.围手术期应用针刺调神方能够在一定程度上抑制术后血清IL-6、IL-10水平升高,从而证明针刺减轻了术后炎症应激反应,这对预防术后感染、防治术后各种并发症及改善患者的预后有重要意义。
     4.围手术期应用针刺调神方能够在一定程度上控制血浆MDA波动幅度,抑制术后血浆NO水平降低,从而证明针刺缓解了术后机体氧化应激反应,改善了组织血供,这有助于防治术后组织、器官缺血缺氧性损害。
     5.围手术期应用针刺调神方对手术患者焦虑、抑郁心理应激有良好的调节作用,这能够改善患者术后心理状况,有利于促进术后机体生理功能恢复及预防术后感染。
     6.动物实验表明:围手术期应用针刺调神方在一定程度上减轻了手术应激反应给机体带来的继发性损害,并且同时增强了机体在应激反应时抵抗损害、修复创伤的能力,这对促进机体术后恢复及改善预后有重要意义。
     综上所述,围手术期应用针刺调神方对手术应激反应多个方面均有良好的调节作用。
Object ive
     1.To observe effects of acupuncture in perioperative period on cardiopulmonary, gastrointestinal functions and analgesia for surgical patients.
     2. To discuss effects of acupuncture in perioperative period on stress response, including inflammatory response, oxidative stress and psychological stress for surgical patients.
     3. To research mechanisms of acupuncture in perioperative period on stress response for surgical rats.
     Method
     Clinical Study
     1. Grouping Method:60patients who scheduled for gynecological laparoscopic surgery and met the inclusion criteria were divided randomly into control group (30cases) and acupuncture group (30cases).
     2. Treatment Method:Control group received gynecological postoperative based treatments only; Acupuncture group received both acupuncture and gynecological postoperative based treatments. Acupuncture method: mind-regulation formula with acupuncture which created by Prof. Zhang hong. The points are sishencong(EX-HNl), shenting(GV24), yintang(EX-HN3), bilateral neiguan(P6) and bilateral sanyinjiao (SP6). Course of Treatment: Acupuncture group received acupuncture at time1hour before operation, and2hour,1day,2days,3days after operation,30minutes one time, QD, for5times.
     3. Observation Indexes:(1)The effect of acupuncture in perioperative period on body functions for surgical patients:①Analgesic effect;②Cardiopulmonary function;③Gastrointestinal function;④Adverse reactions and complications after operation.(2) The effect of acupuncture in perioperative period on stress response for surgical patients:the observation indexes are ACTH and Cor in plasma.(3) The effect of acupuncture in perioperative period on acute inflammatory response for surgical patients: the observation indexes are IL-6and IL-10in serum.(4) The effect of acupuncture in perioperative period on oxidative stress for surgical patients: the observation indexes are MDA and NO in plasma.(5) The effect of acupuncture in perioperative period on psychological stress for surgical patients:the observation indexes are SAS and SDS.
     Experimental Study
     1. Grouping Method:30male SPF Sprague-Dawley rats rats were divided randomly into3groups:control group (30cases), operation group (30cases) and operation plus acupuncture group (30cases).
     2. Experimental Procedure:(1) To establish surgical trauma models of rats with partial hepatectomy.(2) Acupuncture method:The points are sishencong(EX-HN1), shenting(GV24), yintang(EX-HN3), bilateral neiguan(P6) and bilateral sanyinjiao (SP6). Electroacupuncture instrument of G6805was used to stimulate the points of bilateral neiguan(P6) and bilateral sanyinjiao (SP6) with dilatational wave,1-2mA in intensity for30minutes. Adjusting the intensity to make muscle vibrating slightly and avoid rats screaming. Operation plus acupuncture group received acupuncture at time1hour before operation, and2hours after operation,30minutes one time, QD, for2times.(3) Drawing tissues:The rats in three groups were sacrificed to separated liver, hippocampus and hypothalamus in the same time when the stress response is the strongest in partial hepatectomy rats, that is12hours after operation., then freezing samples as soon as possible.
     3. Observation Indexes:(1) Liver histopathological examination was used.(2) The expression of GR in liver was detected by using immunohistochemistry assay.(3) The expression of GR mRNA in hippocampal was examined by reverse transcription-PCR (RT-PCR).(4) The expression of CRH mRNA in hypothalamic was examined by reverse transcription-PCR (RT-PCR).
     Results
     Clinical Study
     (1)The effect of acupuncture in perioperative period on body functions for surgical patients
     ①Analgesic effect
     There was no difference in all the parameters between the two groups at6hours after operation. VAS at1day,3days after operation in two groups were significantly lower than those at6hours after operation (P<0.05), and VAS at1day,3days after operation in acupuncture group were significantly lower than those in control group (P<0.05). BCS at1day,3days after operation in two groups were significantly higher than those at6hours after operation (P<0.05), and BCS at3days after operation in acupuncture group were significantly higher than those in control group (P<0.05)
     ②Cardiopulmonary function
     There was no difference in all the parameters between the two groups before operation. SBP after operation in two groups were significantly higher than those before operation (P<0.05). DBP after operation in control group were significantly higher than those before operation (p<0.05). HR after operation in control group were significantly higher than those before operation (P<0.05), and HR after operation in acupuncture group were significantly lower than those in control group (P<0.05). There was no statistically difference in SPO2and RR in both two groups before and after operation, and there was no statistically difference in SPO2and RR between the two groups
     ③Gastrointestinal function
     The time of first exhaust and the time of first defecation after operation in acupuncture group was significantly lower than that in control group (P<0.05)
     ④Adverse reactions and complications after operation.
     No complications were found in both two groups in the observation period, and there was no statistically difference in the incidence of adverse reactions between the two groups.
     (2) The effect of acupuncture in perioperative period on stress response for surgical patients
     There was no difference in all the parameters between the two groups before operation. ACTH, Cor at6hours,1day after operation in two groups were significantly higher than those before operation (P<0.05), and ACTH, Cor at3days after operation in control group were significantly higher than those before operation, too (P<0.05). ACTH, Cor at6hours,1day after operation in acupuncture group were significantly lower than those in control group (P<0.05)
     (3) The effect of acupuncture in perioperative period on acute inflammatory response for surgical patients
     There was no difference in all the parameters between the two groups before operation. IL-6at6hours,1day,3days after operation in two groups were significantly higher than those before operation(P<0.05), and IL-6at6hours,1day,3days after operation in acupuncture group were significantly lower than those in control group (P<0.05). IL-10at6hours,1day after operation in two groups were significantly higher than those before operation (P<0.05), and IL-10at3days after operation in control group were significantly higher than those before operation, too (P<0.05). IL-10at6hours,1day after operation in acupuncture group were significantly lower than those in control group (P<0.05)
     (4) The effect of acupuncture in perioperative period on oxidative stress for surgical patients
     There was no difference in all the parameters between the two groups before operation. MDA at6hours,1day after operation in two groups were significantly higher than those before operation (p<0.05). Although the overall difference between the two groups was not statistically significant, MDA at6hours,1day after operation in acupuncture group were significantly lower than those in control group (P<0.05).NO at6hours,1day,3days after operation in two groups were significantly lower than those before operation (P<0.05), and NO at6hours,1day after operation in acupuncture group were significantly higher than those in control group (P<0.05)
     (5) The effect of acupuncture in perioperative period on psychological stress for surgical patients
     There was no difference in all the parameters between the two groups before operation. SAS, SDS at7days after operation in both groups were significantly lower than those before operation (p<0.05), and SAS, SDS at7days after operation in acupuncture group were significantly lower than those in control group (P<0.05)
     Experimental Study
     (1) Liver histopathological examination
     Control group:Basically normal hepatocy were observed under light microscopy with HE stain. Operation group:The phenomenon of hepatocy swell and balloon-like degeneration were widespread. The fat drops were observed in hepatocytoplasms partially. Operation plus acupuncture group:The phenomenon of hepatocy swell and balloon-like degeneration were partially.
     (2) The expression of GR in liver (immunohistochemistry assay)
     The GR expression of normal hepatocy is high. The GR expression of hepatocy in operation group was significantly lower than that in control group (P<0.05). There was no statistically difference in the GR expression of hepatocy between operation plus acupuncture group and control group.
     (3) The expression of GR mRNA in hippocampal (RT-PCR)
     The GR mRNA expression of hippocampal in both operation group and operation plus acupuncture group was significantly lower than that in control group (P<0.05), and the GR mRNA expression of hippocampal in operation plus acupuncture group was significantly higher than that in operation group (P<0.05)
     (4) The expression of CRH mRNA in hypothalamic (RT-PCR).
     The CRH mRNA expression of hippocampal in both operation group and operation plus acupuncture group was significantly higher than that in control group (P<0.05), and the CRH mRNA expression of hippocampal in operation plus acupuncture group was significantly lower than that in operation group (P<0.05)
     Conelus ion
     1. Mind-regulation formula with acupuncture in perioperative period for surgical patients can effectively relieve postoperative pain, maintain postoperative cardiopulmonary functions, and promote postoperative gastrointestinal function.
     2. Mind-regulation formula with acupuncture in perioperative period for surgical patients can adjust postoperative stress response to reduce the possibility of the secondary damage of excessive stress response.
     3. Mind-regulation formula with acupuncture in perioperative period for surgical patients can adjust postoperative inflammatory stress response to reduce the incidence of infections and complications.
     4. Mind-regulation formula with acupuncture in perioperative period for surgical patients can adjust postoperative oxidative stress to reduce the incidence of ischemia and hypoxia in tissue and organ.
     5. Mind-regulation formula with acupuncture in perioperative period for surgical patients can adjust perioperative psychological stress to improve the patient's psychological condition and prevent postoperative infection.
     6. Animal experiments showed that:In the postoperative stress response, mind-regulation formula with acupuncture in perioperative period for surgical patients can reduce the possibility of the secondary damage, and enhance the ability to resist damages and repair traumas.
     In summary, mind-regulation formula with acupuncture in perioperative period has good regulation on many aspects of stress response for surgical patients.
引文
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