穴位埋线治疗单纯性肥胖病的临床疗效及分子机制研究
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摘要
目的:本文研究穴位埋线疗法治疗单纯性肥胖病及肥胖并发银屑病的临床疗效及分子机制研究。
方法:
1.临床研究：（1）选择84例单纯性肥胖病患者，根据中医学理论，结合临床，辨证分型，确定埋线穴位。每2周埋线一次，共治疗3个月。观察患者体质量指数（BMI）、体脂百分率、体围、皮褶厚度、胰岛素敏感性指数及瘦素、胰岛素、血脂等的变化及相互关系。（2）选择30例肥胖并发银屑病患者，观察治疗前后BMI、腰髋比、体脂百分率的变化；观察治疗前后银屑病皮损面积和严重度（PASI）评分和中医证候积分的变化。
2.动物实验：将普通饲料喂养大鼠作为正常组，挑选经高脂饲料喂养12周体重超过正常大鼠20%者，随机分模型组和埋线组。埋线治疗后，观察各组大鼠饮水量，摄食量及摄食行为，不同部位（心包周围、肾周围、附睾周围）脂肪的重量、肝肾重量及脂肪细胞形态观察；观察治疗后各组大鼠空腹血糖、总胆固醇、甘油三酯和高密度脂蛋白胆固醇等的变化；治疗后肥胖大鼠外周血空腹胰岛素、血清瘦素；使用ELISA和RT-PCR等方法观察穴位埋线对各组肥胖大鼠下丘脑胰岛素、瘦素含量、瘦素受体基因(OB-RbmRNA)表达，观察下丘脑细胞信号转导抑制因子-3(SOCS-3)基因表达，观察外周血清SOCS-3的含量及外周骨骼肌解偶联蛋白（UCP）表达。
结果:
1.临床研究:穴位埋线治疗单纯性肥胖病临床总有效率为84.52%，男性总有效率为88.88%，女性为83.33%，辨证分型中胃肠实热型有效率为91.48%。治疗肥胖并发银屑病PASI评分和中医证候积分治疗前后具显著差异(P<0.05)， PASI和BMI之间存在正相关（P<0.01）。穴位埋线对于单纯性肥胖病患者与肥胖相关的各项指标均有调节作用，包括：体重、体质量指数、体脂百分率、体围、皮褶厚度、腰髋比等肥胖指标治疗前后均有显著差异（P<0.05）；血脂相关指标总胆固醇、甘油三酯、空腹血糖、瘦素、胰岛素治疗后显著下降与治疗前比具有极显著差异（P<0.01），高密度脂蛋白胆固醇、胰岛素敏感性指数治疗后明显回升与治疗前比有显著差异（P<0.05）。
2.动物实验：埋线后大鼠的摄食量、摄水量、体重和Lee’s指数均下降，治疗前后对比统计学有显著性差异(P<0.01)；埋线后大鼠三部位（心包周围、肾周围、附睾周围）脂肪的重量及肝脏重量均有下降，与模型组肥胖大鼠比较有显著性差异(P<0.05)；埋线后大鼠与模型组肥胖大鼠比较脂肪细胞直径、面积、体积均明显减小（P<0.001）；埋线后大鼠空腹血糖、总胆固醇、甘油三酯明显低于模型组肥胖大鼠(P<0.05)；而埋线后大鼠高密度脂蛋白胆固醇与模型组肥胖大鼠差异无显著性(P>0.05)；埋线后大鼠血清瘦素和胰岛素含量较模型组肥胖大鼠明显降低（P<0.05），而下丘脑瘦素和胰岛素含量和脑、血瘦素和胰岛素之比较模型组肥胖大鼠均明显升高(P<0.05)；埋线后大鼠下丘脑OB-RbmRNA表达水平与模型组肥胖大鼠比较显著增加(P<0.05)，而SOCS-3mRNA表达水平及血清SOCS-3含量明显减少（P<0.05）；埋线后大鼠骨骼肌UCP2mRNA、UCP3mRNA表达水平增加，与模型组肥胖大鼠比有显著性差异（P<0.05）。
结论：
1、穴位埋线治疗单纯性肥胖病临床总有效率为84.52%，男性优于女性，辨证分型中胃肠实热型优于其它型，穴位埋线治疗肥胖并发银屑病在减轻体重的同时，可显著改善银屑病的皮损。
2、穴位埋线治疗单纯性肥胖在明显减轻患者体重的同时，更重要的是降低了与肥胖相关的临床及实验室指标，如：总胆固醇、甘油三酯、空腹血糖等，表明穴位埋线可改善脂代谢，重塑体形，预防和减少肥胖并发症。
3、本研究表明穴位埋线减肥的机制与调节中枢和外周瘦素、胰岛素、瘦素受体、细胞信号转导抑制因子-3表达水平有关，穴位埋线可改善胰岛素、瘦素血脑转运屏障及胰岛素、瘦素受体后信号传导障碍，进而纠正胰岛素抵抗和瘦素抵抗，提高胰岛素、瘦素生物学效应。
4、穴位埋线可通过上调外周解偶联蛋白基因表达水平，增加肥胖机体的外周产热及能量代谢，进而消耗脂肪，达到减肥的目的。
5、穴位埋线可减小肥胖大鼠白色脂肪细胞直径及体积，促进白色脂肪细胞向棕色脂肪细胞的转化，增加脂肪的产热和代谢，从而减轻体重。
Objectives:
This thesis investigates the clinical effect and molecular mechanism in treatingsimple obesity and obesity complicated by psoriasis with catgut implantation atacupoint
Methods:
1. Clinical research:(1)84patients with simple obesity were chosen, guided by thetheory of traditional Chinese Medicine, combined with clinical sydrome differentiation,selected acupoint dialectically, determined the treatment program, every2weeks,treated the patients clinically for3months, and observed the changes and correlations ofbody mass index, body fat percentage, body girth, skin-fold thickness, insulin sensitivity,leptin, insulin and blood lipid.(2) The author chose30patients with obesity complicatedby psoriasis, observed the effects on body mass index, waist hip ratio, body fatpercentage, blood lipid, blood sugar, leptin and insulin, and also observed the psoriasisarea and severity index (PASI) score and the change of traditional chinese medicine(TCM) syndrome integral before and after treatment.
2. Experiments on animals: The author categorized rats fed by standard diet as thenormal group, and divided experimental obese rats (who were fed by high fat diet formore than12weeks and whose weights exceeded20%of those fed by standard diet)randomly into the model group and catgut implanting group. The author observed thethe amount of water consumed, food intake, feeding behavior, fat weights in differentparts (pericardium, perinephrium, epididymis), weights of liver and kidney weights andfat cell morphology, also observed fasting blood sugar, total cholesterol, triglyeerideand high density lipoprotein cholesterol after treatment in different groups, and obeserats' blood fasting insulin and serum leptin. The author observed the effects of catgut implantation at acupoint on obese rats' hypothalamic insulin, leptin content, leptinreceptor gene (OB-RbmRNA) expression, hypothalamic suppressor of cytokinesignaling (SOCS-3) expression, content of peripheral serum (SOCS-3) and peripheralskeletal muscle uncoupling protein(UCP)expression by means of ELISA and RT-PCR.
Results:
1. Clinical research: The total clinical effective rate of the treatment of catgutimplantation at acupoint for simple obesity is84.52%, with88.88%of male and83.33%of female, the effective rate of syndrome differentiation of patients with thestomach and intestine excess-heat type is91.48%. PASI of the treatment of obesitycomplicated with psoriasis and TCM syndrome score before and after the treatment havesignificant difference (P<0.05), there is a positive correlation between PASI and body massindex (P<0.01). Catgut implantation at acupoint can regulate each obesity-related index ofpatients with simple obesity, including body weight, body mass index, body fat percentage,body girth, skin-fold thickness, waist hip ratio, etc. Obesity indexes have significantdifference before and after the treatment (P<0.05); Blood lipid-related indicators (totalcholesterol, triglyeeride, fasting blood sugar, leptin, insulin) declined significantly aftertreatment, compared with those before the treatment, there was a very significant difference(P<0.01), high density lipoprotein cholesterol, insulin sensitivity index got improvedobviously after the treatment and there was a significant difference (P<0.05).
2. Experiments on animals: After the treatment of catgut implantation at acupoint,the rats' food intake and water intake, body weight and Lee's index declined, there wasstatistically significant difference before and after the treatment (P<0.01); After thetreatment, the fat mass and the liver weight of the rats' three parts (pericardium,perinephrium, epididymis) declined, compared with the rats in the model group, therewas significant difference (P<0.05); Compared with the rats in the model group, the fatcell diameter, area and volume of the rats in catgut implanting group were significantlydecreased (P<0.001); The rats' content of fasting blood sugar, triglyeeride and totalcholesterol in catgut implanting group were significantly lower than those in the modelgroup (P<0.05); There was no significant difference between high density lipoproteincholesterol of the rats in catgut implanting group and those in the model group (P>0.05);The content of serum leptin, insulin of the rats in catgut implanting group decreasedsignificantly compared with those in model group(P<0.05), while the content ofhypothalamus leptin and insulin and the ratio increased significantly, compared withthose in the model group (P<0.05); The rats' hypothalamus OB-RbmRNA expression level in the catgut implanting group increased significantly compared with those in themodel group rats (P<0.05), while the SOCS-3mRNA expression level and SOCS-3content in serum decreased significantly (P<0.05); The rats' skeletal muscleUCP2mRNA, UCP3mRNA expression level in the catgut implanting group increasedsignificantly, compared with those in the model group (P<0.05).
Conclusions:
1、The total clinical effective rate of the treatment of catgut implantation atacupoint for simple obesity is84.52%, this treatment has better effects on male patientsthan on female patients and patients with stomach heat type have comparatively bettereffects. The treatment can reduce patients' weight of obesity complicated by psoriasiseffectively, and at the same time, significantly improve the skin lesions of psoriasis.
2、The treatment of catgut implantation at acupoint for simple obesity can reducepatients' weight and at the same time, more importantly,it reduces the clinical andlaboratory indicators associated with obesity, such as, total cholesterol, triglyeeride,fasting blood sugar, etc, which suggests that the treatment can improve lipid metabolism,reshape figure and prevent and reduce complications of obesity.
3、The study has shown that the weight loss mechanism of catgut implantation atacupoint has a correlation with the regulation of the central and peripheral leptin, insulin,OB-Rb, SOCS-3expression level. This treatment can improve insulin, leptin bloodbrain transport barrier and insulin, leptin receptor signal transduction disorder andcorrect insulin and leptin resistance, and improve the insulin and leptin biology effect.
4、The treatment of catgut implantation at acupoint can up-regulate peripheralUCPmRNA gene expression, increase obese organism's peripheral heat production andenergy metabolism, and increase fat burning and help achieve the purpose of weight loss.
5、The treatment of catgut implantation at acupoint can shrink obese rats' thediameter and volume of white fat cells, promote the conversion of white fat cells intobrown ones, and increase the heat production and metabolism of fat so as to lose weight.
方法:
1.临床研究：（1）选择84例单纯性肥胖病患者，根据中医学理论，结合临床，辨证分型，确定埋线穴位。每2周埋线一次，共治疗3个月。观察患者体质量指数（BMI）、体脂百分率、体围、皮褶厚度、胰岛素敏感性指数及瘦素、胰岛素、血脂等的变化及相互关系。（2）选择30例肥胖并发银屑病患者，观察治疗前后BMI、腰髋比、体脂百分率的变化；观察治疗前后银屑病皮损面积和严重度（PASI）评分和中医证候积分的变化。
2.动物实验：将普通饲料喂养大鼠作为正常组，挑选经高脂饲料喂养12周体重超过正常大鼠20%者，随机分模型组和埋线组。埋线治疗后，观察各组大鼠饮水量，摄食量及摄食行为，不同部位（心包周围、肾周围、附睾周围）脂肪的重量、肝肾重量及脂肪细胞形态观察；观察治疗后各组大鼠空腹血糖、总胆固醇、甘油三酯和高密度脂蛋白胆固醇等的变化；治疗后肥胖大鼠外周血空腹胰岛素、血清瘦素；使用ELISA和RT-PCR等方法观察穴位埋线对各组肥胖大鼠下丘脑胰岛素、瘦素含量、瘦素受体基因(OB-RbmRNA)表达，观察下丘脑细胞信号转导抑制因子-3(SOCS-3)基因表达，观察外周血清SOCS-3的含量及外周骨骼肌解偶联蛋白（UCP）表达。
结果:
1.临床研究:穴位埋线治疗单纯性肥胖病临床总有效率为84.52%，男性总有效率为88.88%，女性为83.33%，辨证分型中胃肠实热型有效率为91.48%。治疗肥胖并发银屑病PASI评分和中医证候积分治疗前后具显著差异(P<0.05)， PASI和BMI之间存在正相关（P<0.01）。穴位埋线对于单纯性肥胖病患者与肥胖相关的各项指标均有调节作用，包括：体重、体质量指数、体脂百分率、体围、皮褶厚度、腰髋比等肥胖指标治疗前后均有显著差异（P<0.05）；血脂相关指标总胆固醇、甘油三酯、空腹血糖、瘦素、胰岛素治疗后显著下降与治疗前比具有极显著差异（P<0.01），高密度脂蛋白胆固醇、胰岛素敏感性指数治疗后明显回升与治疗前比有显著差异（P<0.05）。
2.动物实验：埋线后大鼠的摄食量、摄水量、体重和Lee’s指数均下降，治疗前后对比统计学有显著性差异(P<0.01)；埋线后大鼠三部位（心包周围、肾周围、附睾周围）脂肪的重量及肝脏重量均有下降，与模型组肥胖大鼠比较有显著性差异(P<0.05)；埋线后大鼠与模型组肥胖大鼠比较脂肪细胞直径、面积、体积均明显减小（P<0.001）；埋线后大鼠空腹血糖、总胆固醇、甘油三酯明显低于模型组肥胖大鼠(P<0.05)；而埋线后大鼠高密度脂蛋白胆固醇与模型组肥胖大鼠差异无显著性(P>0.05)；埋线后大鼠血清瘦素和胰岛素含量较模型组肥胖大鼠明显降低（P<0.05），而下丘脑瘦素和胰岛素含量和脑、血瘦素和胰岛素之比较模型组肥胖大鼠均明显升高(P<0.05)；埋线后大鼠下丘脑OB-RbmRNA表达水平与模型组肥胖大鼠比较显著增加(P<0.05)，而SOCS-3mRNA表达水平及血清SOCS-3含量明显减少（P<0.05）；埋线后大鼠骨骼肌UCP2mRNA、UCP3mRNA表达水平增加，与模型组肥胖大鼠比有显著性差异（P<0.05）。
结论：
1、穴位埋线治疗单纯性肥胖病临床总有效率为84.52%，男性优于女性，辨证分型中胃肠实热型优于其它型，穴位埋线治疗肥胖并发银屑病在减轻体重的同时，可显著改善银屑病的皮损。
2、穴位埋线治疗单纯性肥胖在明显减轻患者体重的同时，更重要的是降低了与肥胖相关的临床及实验室指标，如：总胆固醇、甘油三酯、空腹血糖等，表明穴位埋线可改善脂代谢，重塑体形，预防和减少肥胖并发症。
3、本研究表明穴位埋线减肥的机制与调节中枢和外周瘦素、胰岛素、瘦素受体、细胞信号转导抑制因子-3表达水平有关，穴位埋线可改善胰岛素、瘦素血脑转运屏障及胰岛素、瘦素受体后信号传导障碍，进而纠正胰岛素抵抗和瘦素抵抗，提高胰岛素、瘦素生物学效应。
4、穴位埋线可通过上调外周解偶联蛋白基因表达水平，增加肥胖机体的外周产热及能量代谢，进而消耗脂肪，达到减肥的目的。
5、穴位埋线可减小肥胖大鼠白色脂肪细胞直径及体积，促进白色脂肪细胞向棕色脂肪细胞的转化，增加脂肪的产热和代谢，从而减轻体重。
Objectives:
This thesis investigates the clinical effect and molecular mechanism in treatingsimple obesity and obesity complicated by psoriasis with catgut implantation atacupoint
Methods:
1. Clinical research:(1)84patients with simple obesity were chosen, guided by thetheory of traditional Chinese Medicine, combined with clinical sydrome differentiation,selected acupoint dialectically, determined the treatment program, every2weeks,treated the patients clinically for3months, and observed the changes and correlations ofbody mass index, body fat percentage, body girth, skin-fold thickness, insulin sensitivity,leptin, insulin and blood lipid.(2) The author chose30patients with obesity complicatedby psoriasis, observed the effects on body mass index, waist hip ratio, body fatpercentage, blood lipid, blood sugar, leptin and insulin, and also observed the psoriasisarea and severity index (PASI) score and the change of traditional chinese medicine(TCM) syndrome integral before and after treatment.
2. Experiments on animals: The author categorized rats fed by standard diet as thenormal group, and divided experimental obese rats (who were fed by high fat diet formore than12weeks and whose weights exceeded20%of those fed by standard diet)randomly into the model group and catgut implanting group. The author observed thethe amount of water consumed, food intake, feeding behavior, fat weights in differentparts (pericardium, perinephrium, epididymis), weights of liver and kidney weights andfat cell morphology, also observed fasting blood sugar, total cholesterol, triglyeerideand high density lipoprotein cholesterol after treatment in different groups, and obeserats' blood fasting insulin and serum leptin. The author observed the effects of catgut implantation at acupoint on obese rats' hypothalamic insulin, leptin content, leptinreceptor gene (OB-RbmRNA) expression, hypothalamic suppressor of cytokinesignaling (SOCS-3) expression, content of peripheral serum (SOCS-3) and peripheralskeletal muscle uncoupling protein(UCP)expression by means of ELISA and RT-PCR.
Results:
1. Clinical research: The total clinical effective rate of the treatment of catgutimplantation at acupoint for simple obesity is84.52%, with88.88%of male and83.33%of female, the effective rate of syndrome differentiation of patients with thestomach and intestine excess-heat type is91.48%. PASI of the treatment of obesitycomplicated with psoriasis and TCM syndrome score before and after the treatment havesignificant difference (P<0.05), there is a positive correlation between PASI and body massindex (P<0.01). Catgut implantation at acupoint can regulate each obesity-related index ofpatients with simple obesity, including body weight, body mass index, body fat percentage,body girth, skin-fold thickness, waist hip ratio, etc. Obesity indexes have significantdifference before and after the treatment (P<0.05); Blood lipid-related indicators (totalcholesterol, triglyeeride, fasting blood sugar, leptin, insulin) declined significantly aftertreatment, compared with those before the treatment, there was a very significant difference(P<0.01), high density lipoprotein cholesterol, insulin sensitivity index got improvedobviously after the treatment and there was a significant difference (P<0.05).
2. Experiments on animals: After the treatment of catgut implantation at acupoint,the rats' food intake and water intake, body weight and Lee's index declined, there wasstatistically significant difference before and after the treatment (P<0.01); After thetreatment, the fat mass and the liver weight of the rats' three parts (pericardium,perinephrium, epididymis) declined, compared with the rats in the model group, therewas significant difference (P<0.05); Compared with the rats in the model group, the fatcell diameter, area and volume of the rats in catgut implanting group were significantlydecreased (P<0.001); The rats' content of fasting blood sugar, triglyeeride and totalcholesterol in catgut implanting group were significantly lower than those in the modelgroup (P<0.05); There was no significant difference between high density lipoproteincholesterol of the rats in catgut implanting group and those in the model group (P>0.05);The content of serum leptin, insulin of the rats in catgut implanting group decreasedsignificantly compared with those in model group(P<0.05), while the content ofhypothalamus leptin and insulin and the ratio increased significantly, compared withthose in the model group (P<0.05); The rats' hypothalamus OB-RbmRNA expression level in the catgut implanting group increased significantly compared with those in themodel group rats (P<0.05), while the SOCS-3mRNA expression level and SOCS-3content in serum decreased significantly (P<0.05); The rats' skeletal muscleUCP2mRNA, UCP3mRNA expression level in the catgut implanting group increasedsignificantly, compared with those in the model group (P<0.05).
Conclusions:
1、The total clinical effective rate of the treatment of catgut implantation atacupoint for simple obesity is84.52%, this treatment has better effects on male patientsthan on female patients and patients with stomach heat type have comparatively bettereffects. The treatment can reduce patients' weight of obesity complicated by psoriasiseffectively, and at the same time, significantly improve the skin lesions of psoriasis.
2、The treatment of catgut implantation at acupoint for simple obesity can reducepatients' weight and at the same time, more importantly,it reduces the clinical andlaboratory indicators associated with obesity, such as, total cholesterol, triglyeeride,fasting blood sugar, etc, which suggests that the treatment can improve lipid metabolism,reshape figure and prevent and reduce complications of obesity.
3、The study has shown that the weight loss mechanism of catgut implantation atacupoint has a correlation with the regulation of the central and peripheral leptin, insulin,OB-Rb, SOCS-3expression level. This treatment can improve insulin, leptin bloodbrain transport barrier and insulin, leptin receptor signal transduction disorder andcorrect insulin and leptin resistance, and improve the insulin and leptin biology effect.
4、The treatment of catgut implantation at acupoint can up-regulate peripheralUCPmRNA gene expression, increase obese organism's peripheral heat production andenergy metabolism, and increase fat burning and help achieve the purpose of weight loss.
5、The treatment of catgut implantation at acupoint can shrink obese rats' thediameter and volume of white fat cells, promote the conversion of white fat cells intobrown ones, and increase the heat production and metabolism of fat so as to lose weight.
引文
[1]邹大进.实用临床肥胖病学.北京：中国医药科技出版社.1999,71-78
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