摘要
一、研究目的
1.通过对糖尿病前期及早期糖尿病人群四诊信息的采集,研究IGR及早期DM中医证候分布特点,采用统计学方法将二者进行比较,初步探讨IGR发展为DM的病机特点。进一步探讨糖尿病的始发病机,明确病性与病位。
2.探讨早期DM六经辨证分布特点及六经辨证思路。
3.观察从六经辨证的三阴入手,采用扶阳护阴,运转枢机法对IGR大鼠糖脂代谢及氧化应激等指标的影响,探讨该法对糖尿病前期的干预疗效及机制。
二、研究内容与方法
1.临床部分:采集2006年末到2007年末广州地区50例单纯糖尿病前期即糖调节受损患者和60例病程小于一年单纯糖尿病患者的中医四诊信息,分别对二者的临床症状、舌象、脉象、证候分布进行频次统计与分析,总结证候分布规律及特点,分析病性及病位。对二者的证候(包括气血阴阳虚证、脏腑虚证、实证)进行卡方比较分析。对60例单纯早期糖尿病患者的症状进行六经辨证分析。
2.实验部分:将SPF级雌性SD大鼠采用高热量饮食加小剂量STZ腹腔注射的方法复制IGR大鼠。将模型成功的IGR大鼠随机分组与正常组共4组:正常组、模型组、中药组、西药组,中药组按生药19.17g/kg·d灌胃,西药组以盐酸二甲双胍0.0225g/kg·d灌胃,正常组及模型组均用等量生理盐水灌胃,观察时间为4周。检测各组大鼠空腹血糖、血脂(TC、TG、HDL-C、LDL-C)、游离脂肪酸、胰岛素水平及胰岛素敏感指数与抵抗指数;血清、胰腺组织氧化应激状态与抗氧化酶水平,包括血清及胰腺组织SOD、MDA、CAT的检测及血清T-AOC、GSH、GSH-PX、VC、VE、N0、NOS的活力或含量等指标;光镜下观察胰腺组织形态变化。
三、研究结果
1.糖尿病前期证候分布情况为肾虚证(50.00%)、气郁证(41.30%)、痰湿证(26.09%)、肝虚证(26.09%)、脾虚证(23.91%)、阳虚证(17.39%)、血瘀证(10.87%)。既可有单纯虚证,也可有单纯实证,虚证是实证的1.5倍,虚实夹杂证最多。早期糖尿病证候分别情况为肾虚证(53.45%)、阳虚证(51.72%)、心虚证(37.93%)肝虚证(34.48%)、脾虚证(31.03%)、气郁证(22.41%)、血瘀证(20.69%)、气虚证(13.79%)、燥热证(13.79%)、胃肠热结证(10.34%)、湿热困脾证(10.34%)。虚证是实证的2.87倍。实证在同一病例中,均与虚证共同出现,而无单独出现者。经卡方检验,早期糖尿病阳虚证、心虚证明显多于糖尿病前期(P<0.01)。糖尿病前期气郁证、痰湿证多于早期糖尿病(P<0.05),早期糖尿病血瘀证、燥热证、胃肠热结证、湿热困脾证较糖前期有加重趋势,但无显著性差异(P>0.05)。
2.早期糖尿病六经辨证分布情况为少阴病(55%)、厥阴病(26.67%)、太阴病(23.33%)、阳明热病(23.33%)、少阳病(20%)、阳明寒病(10%)、太阳病(0%)。
3.与正常组相比,模型组大鼠血糖、甘油三脂、血清游离脂肪酸升高(P<0.05);胰岛素含量升高、胰岛素敏感指数降低、抵抗指数升高(P<0.05);血清MDA、T-AOC、GSH含量升高(P<0.05),VC含量降低(P<0.05),NO、NOS含量升高(P<0.05),胰腺CAT活力降低(P<0.05)。模型组大鼠胰岛萎缩,胞浆不丰富,少数细胞可见空泡变性,胰岛内可见炎症细胞浸润。
4.与模型组比较,中药组大鼠空腹血糖、甘油三脂水平、胰岛素含量、胰岛素抵抗指数降低(P<0.05),敏感指数升高(P<0.05),与西药组无显著性差异(P>0.05);游离脂肪酸水平降低(P<0.05),与西药组有显著性差异(P<0.05)。血清SOD、CAT、GSH-PX活力、VC水平升高(P<0.05),NOS活力、胰腺组织MDA含量降低(P<0.05),二甲双胍在上述方面无作用。血清MDA含量降低,T-AOC含量升高,与西药组无显著性差异(P>0.05),血清NO降低(P<0.05),与西药组有显著性差异(P<0.05)。中药组大鼠胰岛较饱满,细胞数量增多,胞浆较丰富,细胞空泡变性不明显,炎症细胞浸润明显减少。在减轻胰岛炎症细胞浸润、及增加细胞数量方面优于西药组。
四、结论
1.糖尿病前期可从虚致病,也可从实致病,虚者多于实者。虚证主要以肾虚、肝虚、脾虚脏虚为主,气血阴阳虚证不占主导地位,但已初步显露阳虚苗头。实证以气郁、痰湿为多。糖尿病从虚而发。虚证主要为肾虚、心虚、肝虚、脾虚,且以阳虚证为主。实证以气郁、血瘀、燥热、胃肠热结、湿热困脾为主。
2.由糖尿病前期发展到糖尿病是一个由阴证多阳证少发展到阴证的阶段,一个由虚证、实证发展到虚证的阶段。糖尿病发病要以五脏虚损,尤其是肾虚、肝虚、脾虚为基础,在此基础上,阳虚证及心虚证的加重起到了至关重要的作用。
3.糖尿病六经辨证以三阴病为本,少阴病、厥阴病、太阴病,三阴可相合为病。标证可为阳明病(包括阳明热病与阳明寒病)与少阳病。
4.从三阴干预IGR大鼠,扶阳护阴、运转枢机法中药复方具有一定纠正糖脂代谢紊乱,减轻脂毒性,降低胰岛素抵抗的作用。尤其在降低脂毒性方面疗效优于二甲双胍。在组织形态方面,可减轻胰腺组织病理损害,明显减轻胰岛炎症细胞浸润,增加细胞数量及胞浆含量。
5.扶阳护阴、运转枢机法中药复方尤其在氧化应激方面,能明显减少血清中的活性氧簇与活性氮簇;减轻脂质过氧化,减轻机体细胞受自由基攻击的程度;升高抗氧化酶含量与活性,增强机体抗氧化防御系统的能力,疗效优于二甲双胍,具有西药无可比拟的优势。
Objective
1. To investigate the distributive feature of TCM Syndrome in patients with impaired glucose regulation and diabetes through the information collection of four diagnostic methods. Using of statistical methods to compare the two syndromes. Thus discuss the TCM pathogenesis characteristic from IGR developing to DM. To further explore the primary pathogenesis as well as nail down the location and nature of the disease.
2. Probing into the distributive feature of six-channel syndrome differentiation of DM. Discussing the idea of six-channel syndrome differentiation of the disease.
3. Observing the therapeutic effect based on Taiyin, Shaoyin and Jueyin syndrome differentiation. Investigating the effects of the method of strengthen yang and protect yin, circumrotate shuji(SPC) on the disorder of sugar and fat metabolism as well as Oxidative Stress of IGR rats .Discussing the therapeutic mechanism of the treating method to pre-diabetes.
Methods
1. Clinical research: Collecting the information of four diagnostic methods of 50 cases of pure pre-diabetic patients and 60 cases of pure diabetes whose course of disease is less than one year in Guangzhou from the end of 2006 to the end of 2007.. The frequency statistics and Analysis of the two clinical symptoms, the tongue, the pulse and the syndromes distribution were performed separately. Summarizing the distribution rule and the characteristic, and analyzing the nature and the location of the disease. To their syndromes, including deficiency of qi, blood, yin and yang and deficiency of zang-fu organs as well as excess made X2 test. To early diabetes going along six-channel syndrome differentiation.
2. In the experimental study, SPF female SD rats were selected. The IGR rats were made by 4 weeks high fat feeding and injecting small dose STZ. The rats were randomly assigned to four groups: normal group, model group, western medicine(MHT) group with dosage (0. 0225g·kg-1·d-1 by gavage) and TCM group with APC complex prescription (19. 17g·kg-1·d-1 by gavage) . The course of treatment lasted 4 weeks. Observing the effects on blood glucose, blood fat, FFA, insulin, ISI and the index of Oxidative Stress, for example SOD ,MDA, GSH-Px and so on. The effects on morphology of pancreas were analyzed by HE and observed by light microscopy.
Results
1. Pre-diabetic syndrome distribution were as follows , kidney deficiency (50.00%), stagnation of qi (41.30%) , phlegm and dampness syndrome(26. 09%), liver deficiency (26.09%) , spleen deficiency (23.91 %)Yang deficiency (17. 39%)、blood stasis (10. 87%). Simple deficiency syndrome and simple excess syndrome were existed at the same time and the former was 1. 5 times the latter. Early DM syndrome distribution included kidney deficiency (53.45%)、Yang deficiency (51. 72%)、heart deficiency(37.93%) , liver deficiency (34.48%)、spleen deficiency (31.03%)、stagnation of qi (22. 41%)、blood stasis (20. 69%)、qi deficiency (13. 79 %) .deficiency syndrome was 2.87 times the excess syndrome. The excess syndrome existed always with deficiency syndrome in one case. Compared with pre-diabetes, yang deficiency and heart deficiency syndrome in early DM were much more obviously (P<0. 01) . While stagnation of qi and phlegm and dampness syndrome were more than those in DM (P<0. 05) .
2. The distribution of six-channel syndrome differentiation of early DM were as follows, shaoyin disease (55%)、jueyin disease (26.67%)、taiyin disease (23.33%)、heat syndrome of yangming disease (23.33%)、shaoyang disease (20%)、cold syndrome of yangming disease (10%)、taiyang disease (0%) .
3. Compared with normal group, the blood glucose , TG , FFA and insulin, Homa-IR of model rats increased (P < 0.05); ISI decreased (P < 0. 05); MDA, T-AOC, GSH and NO, NOS of blood serum increased. (P < 0. 05), VC was decreased(P< 0. 05), CAT livingness of pancreas was fall (P< 0. 05)。. Pancreas islands and the plasm of cell of model rats were shrinking, and inflammation cell soakage, cell denaturalization.
4. Compared with model group, the blood glucose, TG, insulin, HOMA-IR, T-AOC of TCM group rats were decreased (P < 0. 05), ISI, MDA was increased (P < 0.05), compared with MH group, there was no difference (P>0. 05) ; while FFA and NO of TCM group decreased(P< 0. 05) and the effects were significantly better than MH group (P< 0. 05). SOD、CAT、GSH-PX、VC were increased (P < 0. 05), NOS, MDA of pancreas lower (P < 0. 05), while there were no effects on those in MH group. In TCM group, pancreas islands is satiation , the plasm of cell is more abundant, inflammation cells were much more lessened, the amount of cell manifold and the effects is excelled than MH group.
Conclusions
1. Pre-diabetes can be caused by deficiency, also can be caused by excess. The former is more than the latter. Deficiency syndrome mainly included kidney deficiency, liver deficiency and spleen deficiency. The deficiency syndrome of qi, blood, yin and yang did not occupy the dominant position, but the deficiency of yang had revealed symptom initially. Excess syndrome mainly included stagnation of qi phlegm and dampness syndrome. DM caused by deficiency. Deficiency syndrome mainly included kidney deficiency, heart deficiency, liver deficiency and spleen deficiency. And the deficiency of yang occupied the majority.
2. Diabetes' occurrence take the deficiency of five internal organs, especially the kidney weakness, the liver weakness and spleen weakness as the foundation. The aggravation of yang and heart deficiency played a very important role.
3. The essence of DM by six-channel syndrome differentiation was shaoyin, jueyin and taiyin have had the pathological change. The three can be sick together. Yangming disease and shaoyang disease are the secondary of the disease.
4. The method of strengthen yang and protect yin, circumrotate shuji(SPC) has a certain effect on rectifying the metabolic disorder of sugar and fat, Reducing the fat toxicity and insulin resistance. Especially on reducing fat toxicity aspect, its curative effect significantly surpasses MH. The method can ameliorate pathologic change of pancreatic tissue and relieving inflammatory cell soakage obviously, raising the amounts and cytoblastema content of islet cells.
5. The method of SPC can improve oxidative stress availably. It also can eliminate ROS and RNS, reduce over-oxidation of lipid and debase the damaging degree of the free radical to organism cell. Elevating the content and activeness of anti-oxidase also enhancing organism oxidation resistance defense system' s ability . The curative effect surpasses MH and it has the western medicine incomparable superiority.
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