芍药甘草汤加味对慢性前列腺炎疼痛症状的临床观察及止痛机理研究
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摘要
目的：运用芍药甘草汤加味治疗前列腺炎的疼痛症状,通过临床观察和实验研究探讨芍药甘草汤加味缓解和消除疼痛症状、抑制和修复炎症的药理机制。
方法：临床研究将资料齐全的120例瘀阻型前列腺炎疼痛患者按随机对照法,分为观察组60例,对照组60例,分别给予芍药甘草汤加味和塞来昔布治疗,连服三周,系统观察前列腺炎疼痛症的中医辨证评分、症状评分的变化情况；结合临床检验,观察分析上述两药对前列腺液部分有关参数的影响；实验研究①采用实验小鼠乙酸腹腔注射法,观察实验小鼠15min内扭体次数,并计算扭体抑制率观察芍药甘草汤加味对乙酸致小鼠疼痛的影响。②采用甲醛-巴豆油(8：2)混合致炎、致痛液大鼠前列腺腹叶注射法,制作前列腺炎疼痛模型,按实验要求设立6组,即空白对照组、模型对照组、芍药甘草汤加味高、中、低剂量组、塞来昔布组,连续给药10天,采用病理组织切片法,观察实验大鼠前列腺病理组织学变化；采用逆转录-聚合酶链反应(RT-PCR)方法扩增cDNA,结合图像分析软件分析凝胶图像检测NGFmRNA显色条带的灰度值,观察前列腺组织中NGFmRNA表达的变化；③将实验小鼠随机分为空白对照组、模型对照组、芍药甘草汤加味高、中、低剂量组、塞来昔布组,连续给药7天,与最后一次给药后1小时,采用小鼠尾静脉注射伊文思蓝(2%),并同时腹腔注射0.6%乙酸法,处死动物,收取腹腔液及脊髓。用酶标法测定吸收度,观察芍药甘草汤加味对实验小鼠毛细血管通透性的影响以及脊髓NO活性变化。
结果：①芍药甘草汤加味治疗组患者前列腺疼痛症状评分和辨证评分均明显降低(P<0.01),前列腺液WBC、PH明显改善(P<0.05)②芍药甘草汤加味高剂量组能明显降低实验大鼠前列腺液WBC水平(P<0.01)、提高前列腺液卵磷脂小体密度(P<0.01)；③芍药甘草汤加味能有效抑制乙酸致痛小鼠的扭体次数；④芍药甘草汤加味能有效改善实验小鼠毛细血管通透性(P<0.01),高、中剂量组明显抑制脊髓中NO生物活性(P<0.01)；⑤芍药甘草汤加味高、中剂量组和对照组较模型对照组NGF的表达明显降低(P<0.01),低剂量组(P<0.05)。
结论：
1.芍药甘草汤加味能有效缓解前列腺痛的疼痛症状,其活瘀通络、缓痉止痛作用可能与降低前列腺液中WBC水平,改善前列腺液PH,抑制和消除炎症反应有关；
2.芍药甘草汤加味能减少致痛实验小鼠的扭体次数,对致痛实验小鼠有明显镇痛作用。
3.芍药甘草汤加味的活瘀止痛作用与改善前列腺病理组织的充血、水肿状态,恢复前列腺的正常分泌代谢功能有关；
4.芍药甘草汤加味能有效改善实验动物毛细血管通透性,降低脊髓NO活性,发挥镇痛作用；
5.芍药甘草汤加味可抑制前列腺炎疼痛模型大鼠前列腺组织中NGFmRNA表达,从而发挥其消除炎症反应,缓解疼痛的作用。
Objective:To therapy the prostatic inflammation pain with the addition of peony and liquorice and investigate the Phannaco-mechanism of release and eliminate pain symptom, inhibition and repair inflammation of the addition of peony and liquorice by clinical observation and experimental study.
Methods:Cinical studies:120 patients with full data of Stagnation of the prostatic inflammation pain were divided randomly for 60 patients in the observation group and other 60 patients in the control group to be treated with the addition of peony and liquorice and Celecoxib respectively for 3 weeks then observed the situation of change of syndrome differentiation symptom score of the prostatic inflammation pain systematacia'lly; combined with Clinical Laboratory, observing the effect of two drugs above-mentioned of the parameter of the liquor prostaticus.
Experimental study:①The quantity of body wrest in mice were observed by intraperitoneal injection of acetic acid in mice and calculating the writhing inhibition rate to observe the effect of the addition of peony and liquorice on the acetic acid induced pain in mice. ②Animal models of the prostatic inflammation pain were established by Using Formaldehyde - croton oil (8:2) mixed solution of inflammatory pain induced by injection of rat ventral prostate.The rats were divided to 6 groups of blank controller, model control group, high,medium,low dose,group of the addition of peony and liquorice and Celecoxib group for 10 days. The histological variability of prostate of the rats was observed with histopathology method and the variability of NGFmRNA expression in the prostate was observed by Reverse transcription polymerase chain reaction (RT-PCR) to amplify the cDNA combining image analysis software to analysis Gel document for detecting NGFmRNA color gray value bands;③The mice were divided into blank controller, model control group, high,medium,low dose,group of the addition of peony and liquorice and Celecoxib group for 7 days then administed 1h for the last time then the animals were sacrificed and got the peritoneal fluid and spinal cord with injectioning Evans blue (2%) into the mouse tail vein. The effects of the addition of peony and liquorice on the capillary permeability of the mice and the change of the NO activity in the spinal cord were observed by ELISA determination of absorbance.
Results:①The syndrome differentiation symptom score and the score of the prostatic inflammation pain in the group of the addition of peony and liquorice were Significantly lower and PH of prostatic fluid WBC was significantly improved (P＜0.05);②The level of prostatic fluid WBC of the rats in the high group of the addition of peony was significantly lower (P<0.01) and the density of the prostatic fluid lecithin was increased (P<0.01);③The quantity of body wrest in mice of the acetic acid induced pain can be reduced by the addition of peony and liquorice.④The capillary permeability of mice was improve (P<0.01) in the group of the addition of peony and liquorice and the biological activity of NO of the spinal cord was inhibited in the high,medium dose,group (P<0.01);⑤The expression of NGF was significantly reduced in the high,medium dose,group of the addition of peony and liquorice and the control group compared with the model group (P<0.01), low dose,group (P<0.05)
Conclusion:1. The prostatic inflammation pain can be eased by the addition of peony and liquorice. The promoting blood flow and dredging collaterals effects of the addition of peony and liquorice may relate to the reduction of WBC in the prostatic fluid, the adjustment of the pH of the prostatic fluid and the Inhibition and elimination of the inflammatory reaction.
2. The quantity of body wrest in mice in the induced pain test can be reduced and the analgesic effect significant by the addition of peony and liquorice.
3. The promoting blood flow and analgesic effects of the addition of peony and liquorice relate to the improvement of the hyperemia and edema of prostate pathology and the recovery of the prostate normal secretion metabolism
4. The addition of peony and liquorice can effectively improve the capillary permeability, lower the spinal cord NO activity of experimental animals to educe the Analgesic effect
5. The addition of peony and liquorice can suppress the expressions of the NGFmRNA of prostate tissues of the prostatic inflammation pain model rats to educe the effect of inflammatory reaction elimination and pain relief.
方法：临床研究将资料齐全的120例瘀阻型前列腺炎疼痛患者按随机对照法,分为观察组60例,对照组60例,分别给予芍药甘草汤加味和塞来昔布治疗,连服三周,系统观察前列腺炎疼痛症的中医辨证评分、症状评分的变化情况；结合临床检验,观察分析上述两药对前列腺液部分有关参数的影响；实验研究①采用实验小鼠乙酸腹腔注射法,观察实验小鼠15min内扭体次数,并计算扭体抑制率观察芍药甘草汤加味对乙酸致小鼠疼痛的影响。②采用甲醛-巴豆油(8：2)混合致炎、致痛液大鼠前列腺腹叶注射法,制作前列腺炎疼痛模型,按实验要求设立6组,即空白对照组、模型对照组、芍药甘草汤加味高、中、低剂量组、塞来昔布组,连续给药10天,采用病理组织切片法,观察实验大鼠前列腺病理组织学变化；采用逆转录-聚合酶链反应(RT-PCR)方法扩增cDNA,结合图像分析软件分析凝胶图像检测NGFmRNA显色条带的灰度值,观察前列腺组织中NGFmRNA表达的变化；③将实验小鼠随机分为空白对照组、模型对照组、芍药甘草汤加味高、中、低剂量组、塞来昔布组,连续给药7天,与最后一次给药后1小时,采用小鼠尾静脉注射伊文思蓝(2%),并同时腹腔注射0.6%乙酸法,处死动物,收取腹腔液及脊髓。用酶标法测定吸收度,观察芍药甘草汤加味对实验小鼠毛细血管通透性的影响以及脊髓NO活性变化。
结果：①芍药甘草汤加味治疗组患者前列腺疼痛症状评分和辨证评分均明显降低(P<0.01),前列腺液WBC、PH明显改善(P<0.05)②芍药甘草汤加味高剂量组能明显降低实验大鼠前列腺液WBC水平(P<0.01)、提高前列腺液卵磷脂小体密度(P<0.01)；③芍药甘草汤加味能有效抑制乙酸致痛小鼠的扭体次数；④芍药甘草汤加味能有效改善实验小鼠毛细血管通透性(P<0.01),高、中剂量组明显抑制脊髓中NO生物活性(P<0.01)；⑤芍药甘草汤加味高、中剂量组和对照组较模型对照组NGF的表达明显降低(P<0.01),低剂量组(P<0.05)。
结论：
1.芍药甘草汤加味能有效缓解前列腺痛的疼痛症状,其活瘀通络、缓痉止痛作用可能与降低前列腺液中WBC水平,改善前列腺液PH,抑制和消除炎症反应有关；
2.芍药甘草汤加味能减少致痛实验小鼠的扭体次数,对致痛实验小鼠有明显镇痛作用。
3.芍药甘草汤加味的活瘀止痛作用与改善前列腺病理组织的充血、水肿状态,恢复前列腺的正常分泌代谢功能有关；
4.芍药甘草汤加味能有效改善实验动物毛细血管通透性,降低脊髓NO活性,发挥镇痛作用；
5.芍药甘草汤加味可抑制前列腺炎疼痛模型大鼠前列腺组织中NGFmRNA表达,从而发挥其消除炎症反应,缓解疼痛的作用。
Objective:To therapy the prostatic inflammation pain with the addition of peony and liquorice and investigate the Phannaco-mechanism of release and eliminate pain symptom, inhibition and repair inflammation of the addition of peony and liquorice by clinical observation and experimental study.
Methods:Cinical studies:120 patients with full data of Stagnation of the prostatic inflammation pain were divided randomly for 60 patients in the observation group and other 60 patients in the control group to be treated with the addition of peony and liquorice and Celecoxib respectively for 3 weeks then observed the situation of change of syndrome differentiation symptom score of the prostatic inflammation pain systematacia'lly; combined with Clinical Laboratory, observing the effect of two drugs above-mentioned of the parameter of the liquor prostaticus.
Experimental study:①The quantity of body wrest in mice were observed by intraperitoneal injection of acetic acid in mice and calculating the writhing inhibition rate to observe the effect of the addition of peony and liquorice on the acetic acid induced pain in mice. ②Animal models of the prostatic inflammation pain were established by Using Formaldehyde - croton oil (8:2) mixed solution of inflammatory pain induced by injection of rat ventral prostate.The rats were divided to 6 groups of blank controller, model control group, high,medium,low dose,group of the addition of peony and liquorice and Celecoxib group for 10 days. The histological variability of prostate of the rats was observed with histopathology method and the variability of NGFmRNA expression in the prostate was observed by Reverse transcription polymerase chain reaction (RT-PCR) to amplify the cDNA combining image analysis software to analysis Gel document for detecting NGFmRNA color gray value bands;③The mice were divided into blank controller, model control group, high,medium,low dose,group of the addition of peony and liquorice and Celecoxib group for 7 days then administed 1h for the last time then the animals were sacrificed and got the peritoneal fluid and spinal cord with injectioning Evans blue (2%) into the mouse tail vein. The effects of the addition of peony and liquorice on the capillary permeability of the mice and the change of the NO activity in the spinal cord were observed by ELISA determination of absorbance.
Results:①The syndrome differentiation symptom score and the score of the prostatic inflammation pain in the group of the addition of peony and liquorice were Significantly lower and PH of prostatic fluid WBC was significantly improved (P＜0.05);②The level of prostatic fluid WBC of the rats in the high group of the addition of peony was significantly lower (P<0.01) and the density of the prostatic fluid lecithin was increased (P<0.01);③The quantity of body wrest in mice of the acetic acid induced pain can be reduced by the addition of peony and liquorice.④The capillary permeability of mice was improve (P<0.01) in the group of the addition of peony and liquorice and the biological activity of NO of the spinal cord was inhibited in the high,medium dose,group (P<0.01);⑤The expression of NGF was significantly reduced in the high,medium dose,group of the addition of peony and liquorice and the control group compared with the model group (P<0.01), low dose,group (P<0.05)
Conclusion:1. The prostatic inflammation pain can be eased by the addition of peony and liquorice. The promoting blood flow and dredging collaterals effects of the addition of peony and liquorice may relate to the reduction of WBC in the prostatic fluid, the adjustment of the pH of the prostatic fluid and the Inhibition and elimination of the inflammatory reaction.
2. The quantity of body wrest in mice in the induced pain test can be reduced and the analgesic effect significant by the addition of peony and liquorice.
3. The promoting blood flow and analgesic effects of the addition of peony and liquorice relate to the improvement of the hyperemia and edema of prostate pathology and the recovery of the prostate normal secretion metabolism
4. The addition of peony and liquorice can effectively improve the capillary permeability, lower the spinal cord NO activity of experimental animals to educe the Analgesic effect
5. The addition of peony and liquorice can suppress the expressions of the NGFmRNA of prostate tissues of the prostatic inflammation pain model rats to educe the effect of inflammatory reaction elimination and pain relief.
引文
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