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解毒活血汤治疗ⅢA型前列腺炎疗效观察及对大鼠前列腺组织TNF-α、IL-8、IL-10影响的实验研究
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摘要
[目的]
     1.观察解毒活血汤治疗ⅢA型前列腺炎的临床疗效及对前列腺液中TNF-α、IL-8、IL-10及WBC的影响,探求中医药治疗ⅢA型前列腺炎的作用机理并提供实验依据。
     2.观察解毒活血汤对慢性非细菌性前列腺炎大鼠前列腺组织TNF-α、 IL-8、IL-10的影响。
     [方法]
     1.临床观察:按就诊顺序纳入80名ⅢA型慢性前列腺炎患者,随机分为治疗组(解毒活血汤组)和对照组(舍尼通组),每组40人。治疗组以解毒活血汤口服,每次1袋(150ml),日2次,早晚分服。对照组予以舍尼通片,每次1片,日2次,早晚分服。两组均以8周为一个疗程。所有患者受试前后均使用NIH-CPSI表进行症状评分和中医证侯症状评分。在受试前后,分别收集患者的前列腺液保存。所有受试者临床治疗前后使用EL ISA法检测前列腺液中的TNF-α、IL-8、IL-10含量。
     2.动物实验:从40只雄性SD大鼠中随机抽取30只,去势后,经皮下多点注射苯甲酸雌二醇造成慢性非细菌性前列腺炎动物模型,剩余10只作为空白对照组(正常组)。造模成功后,慢性非细菌性前列腺炎模型大鼠再随机分成模型组、舍尼通组、解毒活血汤组。解毒活血汤组给药量为1g/kg·d(即4ml/d),舍尼通组给药量为0.025mg/kg·d(即4ml/d),正常组、模型组给予相同剂量的蒸馏水。以上各组均灌胃给药,每日一次,连续给药30d。治疗结束后将各组大鼠称重后处死。取前列腺组织,观察其病理改变,用ELISA法测定前列腺组织匀浆TNF-α、IL-8、IL-10的含量。
     [结果]
     1.临床研究:①解毒活血汤能有效治疗ⅢA型CPPS,能够明显改善患者临床症状,有效降低NIH-SCPI积分,能明显改善中医证侯症状积分,能够明显降低EPS中WBC含量。②解毒活血汤能够明显降低患者EPS中TNF-α、IL-8的水平。它对ⅢA型CPPS患者的局部免疫功能有调节作用。③EPS中TNF-α、IL-8、IL-10的含量与NIH-CPSI中疼痛症状积分呈正相关(p<0.05)。
     2.动物实验:①病理观察显示,模型组大鼠前列腺组织表现为慢性炎症的病理变化。其前列腺腺体普遍与周围组织粘连,腺体呈暗红色或棕黄色,质稍硬。显微镜下主要表现为淋巴细胞和单核细胞的浸润,间质水肿及纤维组织增生,前列腺上皮破坏、萎缩及脱落,前列腺管壁的增生或破坏。对前列腺病理切片的分级进行统计分析,显示模型组大鼠与正常大鼠前列腺组织病理表现差异有统计学意义(P<0.01),表明造模成功。②解毒活血汤组大鼠前列腺上皮组织基本恢复正常,管壁结构完整,间质水肿消失。病理分级统计结果显示解毒活血汤组及舍尼通组与模型组比较,差异有统计学意义(P<0.01,P<0.05)。③模型组大鼠前列腺组织TNF-α、IL-8的水平较正常组升高(P<0.01);解毒活血汤组大鼠前列腺组织TNF-α、L-8的水平较模型组明显降低(P<0.01),IL-10的水平较模型组差异无显著性意义(P>0.05)。
     [结论]
     1.解毒活血汤能有效治疗ⅢA型CPPS,能够明显改善患者临床症状,有效降低NIH-SCPI积分,能明显改善中医证侯症状积分,能够明显降低EPS中WBC含量,消除炎症,减轻患者的病痛,是目前值得提倡的治疗方法和临证思维方法。
     2.ⅢA型CPPS,疼痛症状积分与细胞因子TNF-α、IL-8、IL-10呈正相关,可作为ⅢA型CPPS病情和治疗效果制定的主要参考指标。
     3.慢性非细菌性前列腺炎模型大鼠前列腺组织中TNF-α、IL-8、IL-10水平升高,说明细胞因子参与慢性非细菌性前列腺炎发病过程,通过对其调节,能够达到减轻或消除前列腺组织炎症反应,达到治疗作用。
     4.解毒活血汤能够减轻或消除大鼠前列腺组织的炎症反应,修复其破坏的组织结构,对前列腺组织起到明显保护作用。为临床研究提供了实验依据。
     5.解毒活血汤能够降低模型大鼠前列腺组织内促炎性因子TNF-α、 IL-8的水平,从而减轻前列腺组织炎症反应的程度。
Object:1. To explore the mechanism and provide experimental basis of traditional Chinese medicine's treatment in type Ⅲa prostatitis, on the basis of observing the curative effect of the Detoxicating and activating blood Decoction's treatment in type III A prostatitis and its influence inTNF-α、IL-8、 IL-10and WBC in prostatic fluid.
     2. To observe the effect of Detoxicating and activating blood Decoction on TNF-α,IL-8,DL-10in rats prostate tissue with chronic nonbacterial prostatitis.
     Methods:1. The clinical observation:Bring into80type ⅢA patients with chronic prostatitis according to treatment's sequence, divide into the treatment group (Detoxicating and activating blood Decoction group) and the control group (Cernilton group) randomly, n=40. The treatment group take Detoxicating and activating blood Decoction150ml each, twice per day, morning and evening hours service. The Control group take Cernilton slices each one for one pill and twice per day, morning and evening hours service. The two groups are in a course of treatment with eight weeks. All patients use the NIH-CPSI table symptom score before and after the test. Patients'prostatic fluid were collected and saved before and after the treatment.The content of TNF-α、 IL-8、DL-10in all subjects'prostatic fluid should be detected by ELISA before and after the clinical treatment.
     2. Animal experiments:selected30male SD rats from the40ones randomly, castrated and injected subcutaneously with estradiol benzoate and caused to be the animal models of chronic non-bacterial prostatitis. The remaining10as the blank control group (normal group). After the modeling, the chronic non-bacterial prostatitis rat model were divided into model group, Cernilton group and Detoxicating and activating blood soup group randomly. The dosage of Detoxicating and activating blood soup group is1g/kg·d (4ml/d), the Cernilton group's is0.025mg/kg·d (4ml/d),the normal group and the model group were given the same dosage with distilled water. These groups were administered orally, once daily, administered for30d continuously. The rats were killed after weighting at the end of treatment. Take the prostates' issue to observe their pathological changes, measure the content of TNF-α、IL-8、IL-10in homogenates of prostates'tissue by ELISA.
     Results:1. Clinical study:①Detoxicating and activating blood soup can treat type IIIA CPPS effectively, improve patients'clinical symptoms significantly, reduce the points of NIH-SCPI effectively, lessen the TCM syndrome score obviously, decrease the content of the WBC in EPS.②Detoxicating and activating blood soup can significantly reduce the levels of TNF-α IL-8in patients'EPS. It has the localized immune function regulation to type Ⅲa CPPS patients.③The levels of TNF-α、IL-8、IL-10in EPS and the score of pain symptom of the NIH-CPSI was correlated positively (p<0.05).
     2. Animal experiments:①pathological observation show that the pathological changes of the prostate tissue of model group rats are chronic inflammation. The prostate gland generally adhere the surrounding tissue, glands are dark red or brown and its quality are a little stiff. Under the microscope,their performance are mainly lymphocytes and mononuclear cell infiltration, interstitial edema and fibrous tissue hyperplasia, prostate epithelial damage, atrophy and loss, prostate wall hyperplasia or destruction. The statistical analysis of classification of pathological slice of prostate grand biopsy show difference significantly (P<0.01) between model rats and normal rat indicate that the model was successful.②Detoxicating and activating blood soup group rats'prostate epithelial tissue returned to be normal, the wall structural integrity, interstitial edema disappeared. Pathological classification statistics show the difference was statistically significant (P<0.01, P<0.05) among the comparison of the Detoxicating and activating blood soup groups the Cernilton group and the model group.③The levels of TNF-a, IL-8in model group rats'prostate tissue have more increasing than the normal group's (P<0.01); the levels of TNF-a, IL-8in the rats'prostate tissue of the Detoxicating and activating blood soup group compared with the model group's were significantly lower (P<0.01),while the levels of EL-10compared with model group's don't have difference obviously (P>0.05).
     Conclusion:
     1.The treament of Detoxicating and activating blood Decoction can treat type III A CPPS effectively, improve patients'clinical symptoms significantly, reduce the points of NEH-SCPI effectively, lessen the TCM syndrome score obviously, decrease the content of the WBC in EPS, eliminate inflammation and reduce the patient's pain, which is a recommendable treatment method and Clinical Thoughts.
     2.Type Ⅲa CPPS's scores of pain symptom and the cytokine of TNF-α、IL-8、 IL-10were positively related, which can be formulated as the reference index of patient's condition and treatment effective of type IIIA CPPS.
     3. The levels of TNF-α、IL-8、IL-10in prostates'tissue of rat model with chronic non-bacterial prostatitis were increased, which indicate that the cytokines are involved in the incidence of inflammation of chronic non-bacterial prostatitis. We can achieve a therapeutic effect by the mean of its regulation which can alleviate or eliminate the inflammation in the prostates'tissue.
     4.Detoxicating and activating blood Decoction can reduce or eliminate the inflammatory response of rat prostate tissue, improve the destruction of its organizational structure, which play a significant protective effect on prostate tissue and complement the experimental basis for clinical studies.
     5. Detoxicating and activating blood Decoction can reduce the levels of promote inflammatory factor of TNF-a and IL-8in prostates'tissue of the rat model, thereby reducing the extent of inflammation in prostate tissue.
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