Study On Clinic Effect Of "HuoXueXiaoying" Prescription For Nodular Goiter And Its Therapeutic Mechanism

Objective:To explore the Etiology Pathogenesis of nodular goiter (Abbreviation:NG)and the relationship among NG, blood stasis and sputum condensation.To observe the clinical effect of "HuoXueXiaoying" prescription,and to evaluate the clinical value. To detect several cytokines related levels of peripheral blood of patients with NG,and to explore the molecular mechanism of NG'pathogenesis.To observe the related changes in cytokine levels after the treatment of "HuoXueXiaoying" prescription, and to study the mechanism of action in "HuoXueXiaoying" prescription treatment on NG preliminary.Methods:This study was divided into three parts,as follows.1.Theoretical studies:Analysis,sorting out ancient literature,combining with modern clinical treatment experience to compare the knowing of NG'etiology,pathogenesis and the dialectical methods of different physicians;comprehensive analyzing NG'etiology, pathogenesis and the treatment experience of modern medicine to find a breakthrough point for this research.2.Clinical efficacy studies:Used randomized single-blind antithesis,90 NG(blood stasis and sputum condensation type) patients who measure up the standard were divided into 2 groups: experimental group(n=45, to be treated with "HuoXueXiaoying" prescription) and contrast group (n=45,to be treated with euthyrox tablets),3 months for a course of treatment,a total of 2 courses. Then to Observe and analyze comparatively the related indicators (including related symptoms and signs,thyroid nodule size and the maximum diameter and the number of nodules,thyroid function, etc.)before treatment and after treating for 3,6 months.3. Clinical Mechanism studies:Selected 30 nodular goiter patients who had finished 6 months'standard treatment in the second part of the experimental group in this subject and let them be the case group. At the same time selected 30 matched healthy adults in outpatients randomly as normal control group. Quantitative enzyme-linked immunosorbent assay(ELISA)was used to measure the serum levels of vascular endothelial growth factor (VEGF),transforming growth factorβ1(TGF-β1),soluble Fas(sFas) and soluble Fas Ligand(sFasL)of the two groups before treatment and after treating for 3 or 6 months.Radio immunoassay (RIA) was used to determine the serum levels of insulin-like growth factor I(IGF-I),interleukin 10(IL-10),interleukin 6(IL-6)and tumor necrosis factor(TNF)of the two groups before treatment and after treating for 3 or 6 months.Each indicator should be compared with the control group before the treatment in case group,and then the concentrations changes were compared separately after the treatment of "HuoXueXiaoying" prescription. Sub-analysis of four aspects:①The impact "HuoXueXiaoying" prescription do on vascular endothelial growth factor(VEGF) of the patients with NG;②The impact "HuoXueXiaoying" prescription do on patients with NG' growth factors(IGF-I,TGF-β1);③The impact "HuoXueXiaoying" prescription do on apoptotic factors (sFas,sFasL) of the patients with NG;④The impact "HuoXueXiaoying" prescription do on immune factors (IL-1β,IL-6 and TNF)of the patients with NG. Then explore the molecular mechanism of NG'pathogenesis and the mechanism of "HuoXueXiaoying" prescription treatment on patients with NG preliminary.All data were analyzed statistically by SPSS13.0 statistical software. Data used mean±standard deviation (X±S) to express; For groups comparison, use t to test measurement data,use X2 to test count data.Results:1.Theoretical studies have shown that:Nodular goiter belongs to the category of disease "ying" or "ying gall" of traditional Chinese medicine(TCM)in general.Chinese medicine physicians generally think that NG is mainly due to qi stagnation, blood stasis block,phlegm stagnation and qi,sputum,blood cross-resistance formed on the anterior which caused by emotional imbalance, inappropriate water and soil,physical factors and so on. They put the pathogenesis of qi stagnation, blood stasis and sputum condensation to be the causes of nodules.Medication using should be some regular,that is,mainly regulating qi and phlegm, promoting blood circulation, and resolving hard lump. The cause of NG in modern medicine is not clear entirely.It is generally believed that the reasons of pathogenesis is that pituitary TSH secretion increase because of various factors.TSH's stimulating thyroid tissues constantly can result in repeating or lasting thyroid hyperplasia.Repeating thyroid hyperplasia and redintegration in a long-term are under imbalance. Thyroid was separated by fibrous tissue to form a multi-nodular thyroid tissue. More and more researches show any growth factors may be involved in the disease and its pathological process.It is unclear whether the pathogenesis of NG is related to thyroid follicular cells apoptosis.Western medicine treatment on NG is mainly surgery and thyroid hormone suppression therapy,etc.But the both are flawed. So looking for more secure,efficient and convenient therapy is still a significant issue. Nearly a decade of research reports indicated that many traditional Chinese medicine prescription treatments on NG have better efficacy, but most of the study is only about clinical efficacy.It is rarely reported on the mechanism of traditional Chinese medicine treatment.2. Clinical efficacy studies have shown that:When the two courses of the treatment finished, the available statistics was:41 cases of experimental group and 40 patients of contral group.(1)The total effect of two groups were compared:experimental group:The total effective rate was 87.9% for the two courses,was 73.2% for a course of treatment;control group:The total effective rate was 47.5% for the two courses,was 37.5% for a course of treatment; Two groups compared at different times were different significantly(P<0.05).The experimental group always showed higher efficiency than compared group.(2)The relationship between treatment time and effect:Both treatment groups which had two courses of treatment had higer efficacy than those in a course of treatment.(3)After treatment,thyroid volumes and nodule maximum diameters were lower than before.There were significant difference when they were compared in each group separately(P<0.05).Thyriod volumes were not significantly different when they were compared between two groups (P>0.05),and nodules's reduced levels of maximum diameter of the experimental group were more than the control group (P<0.05).(4)The relationship between nodule size and effect of the two groups:After two courses of treatment,the results showed that the efficiency of two groups depend on pre-treatment nodule diameter:less than 2cm> 2-4cm>more than 4cm.(5)Changes in thyroid function before and after treatment of the two groups:Free triiodothyronine(FT3),free thyroxine(FT4) of two groups and sensitive thyrotropin(sTSH) in the experimental group before and after two courses of treatment had no significant difference (P>0.05);After treatment the sTSH of the control group was significantly decreased (P<0.05).(6)Side effects:There was no significantly adverse reaction in the experimental group. In the control group,10 patients had various degrees about dry mouth, irritability, insomnia,and 4 cases in which had palpitations,fever and other symptoms;The rate of its adverse reaction was 25%.3. Clinical mechanism studies have shown that:(1)Serum VEGF level of patients with NG in pre-treatment was higher than that of the control group (P<0.05).After "HuoXueXiaoying" prescription treatment,serum VEGF level was reduced 3 months treatment later,but it had no significant difference compared with that before treatment (P>0.05);After 6 months treatment the level was reduced to normal level,compared with the control group, and there was no statistical significance (P>0.05).(2)Serum IGF-I level of patients with NG in pre-treatment was higher than that of the control group (P<0.05),and serum TGF-β1 level was lower than that of the control group (P<0.05).After "HuoXueXiaoying"prescription treatment,serum IGF-I level was decreased after 3-month treatment,but no statistics significance (P>0.05);After 6 months treatment,it was significantly lower than that before treatment (P<0.05),but there was no significant difference when it was compared with that of the contral group(P >0.05). Serum TGF-β1 level was significantly higher after 3-month treatment(P<0.01));After 6 months treatment,it was decreased obviously,but was still significantly higher than that before treatment (P<0.01),and was also higher than that of the control group (P<0.05).(3)Serum sFas level of patients with NG in pre-treatment was significantly higher than the control group (P<0.01),and serum sFasL level was lower (P<0.05).After "HuoXueXiaoying" prescription treatment,serum sFas levels was a little decreased after 3-month treatment,but no statistics significance(P>0.05); After 6-month treatment,it was significantly lower than that before treatment (P<0.01),but compared with the control group, it was no sinnificantly different (P>0.05).Serum sFasL level was increased obviousely after 3-month treatment(P<0.05);It increased constantly after 6-month treatment,having significant difference compared with that of patients who had 3-month treatment or were under pre-treatment,and was significantly higher than normal level,compared with the control group (P<0.01).(4)Serum IL-1βand TNF levels of patients with NG in pre-treatment were a little higher than those of the control group,compared with those before treatment,but there were no significant differences(P>0.05);Serum IL-6 level was lower than that of the control group (P<0.05).After "HuoXueXiaoying" prescription treatment,Serum IL-1βand TNF levels were increased obviousely after 3-month teratment(P<0.05),and were a little decreased after 6-month treatment(P>0.05);And they were higher than normal level,compared with the control group,having statistical significance(P<0.05).Serum IL-6 level has increased after 3-month treatment,but compared with those before treatment,there was no significant difference (P>0.05);It was significantly increased to normal level after 6-month treatment,it was more significantly different than after 3-month treatment and before treatment (P<0.05),and compared with the control group,there was no significant difference (P>0.05).Conclusion:1.Nodular goiter mainly dues to qi stagnation, blood stasis block,phlegm stagnation and qi,sputum,blood cross-resistance formed on the anterior neck which caused by emotional imbalance, inappraprite water and soil,physical factors and so on. Chinese medicine treatment on NG has achieved better efficacy.It can avoid patient's cardiac rhythm disorders and osteoporosis and other side effects caused by western medicine, especially is suitable for frail patients.2.The total effective rate of "HuoXueXiaoying" prescription treated group was higher than that of euthyrox group; "HuoXueXiaoying" prescription is better than euthyrox on reducing or removing the nodules.It's shown that "HuoXueXiaoying" prescription was more clinically effective than euthyrox on treating NG.Both two groups which had 2 courses of treatment were better than those in a course of treatment.It is closely related between the elimination with size of nodules:the efficacy of treatment on nodule diameter<2cm was better, that of>4cm was in poorer treatment outcomes."HuoXueXiaoying" prescription for the function of thyroid hormone secretion had no significant influence, litter toxic side effects,high security and high performance.3. Growth factors(VEGF, IGF-I,TGF-β1)are closely related to the incidence and prognosis of nodular goiter."HuoXueXiaoying" prescription can suppress the thyroid follicular hyperplasia and thyroid tissue hyperplasia by appropriately reducing serum VEGF, IGF-I levels and increasing serum TGF-β1 level.4.Apoptotic factors (sFas,sFasL)play an important role in the pathogenes and treatment on nodular goiter.There is suppressed apoptos is in NG. "HuoXueXiaoying" prescription probably can induce apoptosis of thyroid cells to shrink goiter and nodule to achieve the purpose of treating NG through reducing serum sFas level and elevating serum sFasL level.5.Immune-regulating factors(IL-1 P,IL-6 and TNF)were also probably involved in the pathogenesis and prognosis process of nodular goiter."HuoXueXiaoying" prescription may be through appropriately increasing the serum IL-1β,TNF and IL-6 levels, inducing apoptosis of thyroid cells and inhibiting proliferation of thyroid follicular to adjust the balance between proliferation and apoptosis of thyroid cell for therapeutic purposes.