Therapeutic Effect Of Yingqiling For Graves Disease And Its Influence On Cell Apoptosis

Chapter 1 Article review of Graves diseaseIn traditional Chinese medical theory, the pathogenesis of Graves disease is relatedwith the impairment of seven emotions, dietary disorder, geographic condition andconstitution. The root pathogenic factor of.Graves disease is yin deficiency, and theincidental pathogenic factors are of fire accumulation, phlegm stagnation and blood stasis.Graves disease is characterized as coexistence of deficiency and excess. The therapeuticprinciples should be tonifying deficiency and purging excess, regulating yin and yangthrough strengthening Qi and nourishing yin, clearing heat and purging fire, dissolvingphlegm and removing stasis, softening hardness and dissipating mass.In modern medical theory, the pathogenesis of Graves disease is related with immunedisorder, genetic factors, neuropsychic damages, dietary and medication, inflammation. Thediagnosis is made according to the clinical manifestations and laboratory examination. Thetreatment of Graves disease includes antithyroid drug therapy, ¹³¹I therapy, surgery andinterventional embolization.The thyroid cell apoptosis in Graves.disease is mediated by Fas/FasL gene. In Gravesdisease patients, the serum sFas level increased and Bel-2 over-expressed, which inhibitedthe cell apoptosis mediated by Fas/FasL gene, promoted the proliferation of thyroid cellsand the secretion of thyroid hormone, thus induce the clinical manifestations. In modernChinese medical theory, cell proliferation is classified into yang and cell apoptosis into yin.Once the balance of proliferation and apoptosis is broken, the syndrome of relativepredominance of yin or yang will be presented. Predominance of yang and decline of yin(hyper-proliferation and apoptosis decrease of the body cells) is the pathophysiologicalbasis of occurrence of tumor and autoimmune diseases. Decline of yang and predominanceof yin (proliferation decrease and apoptosis increase of the body cells) is related withhypo-function disease. The herbal medicine which has the actions of clearing heat andremoving toxicity, activating blood and removing stasis, strengthening Qi and nourishing yin, tonifying blood, strengthening kidney and spleen, softening hardness and dissipatingmass exerts an effect on inducing cell apoptosis.Chapter 2 Research of Yingqiling in the treatment of Graves diseaseObjectiveTo supply evidences for the clinical use, the therapeutic effect of Yingqiling forhyperthyroidism(graves disease)was observed and its therapeutic mechanism wasinvestigated by observing the changes of laboratory indexes and apoptotie factors in thisstudy.Methods1. Inclusion criteria(1) patients aged 18～70 years;(2) being subjected to the diagnostic criteria of hyperthyroidism(graves disease);(3) having a general knowledge of the main pharmacological characteristics andpossible adverse reactions of drugs;(4) not receiving antithyroid drug within 3 months;2. Exclusion criteria(1) Patients being not subjected to the inclusion criteria and patients withhyperthyroidism caused by other diseases such as nodular goiter and thyroid neoplasms;(2) patients with goiter and syndrome group of hypermetabolism caused by simplegoiter, neurosis, autonomy hyperfunctional thyroid nodule; patients with endocrine diseasesand immunity diseases such as thyroiditis, rheumatoid disease, neoplasms, asthma anddiabetes;(3) Pregnant and lactating women patients; patients with hyperthyroidism crisis andpsychotic disorders;(4) patients complicated with serious primary diseases such as cardiovascular disease,cerebrovaseular disease, liver and kidney disease and hematopathy;(5) patients with allergic constitution and multiple drug hypersensitivity;(6) patients falling to receive designed regimen as well as those with incomplete data;3. GroupingEighty patients being subjecting to the inclusion criteria were equally randomized intotwo groups: yingqiling group (treatment group) and methimazole group (control group).The differences of sex, age, disease course, main clinical symptoms and signs, laboratoryindexes were insignificant between the two groups, indicating that the two groups havecomparative conditions.4. Therapeutic methods Treatment group: Yingqiling Tablets, 5 tablets per time, rid for 3 continuous months;Control group: mcthimazole, 10mg per time, tid for 2 continuous months, the dosagewill bc reduced after the symptoms were relieved.5. Therapeutic effect evaluationSymptoms such as palpitation, restlessness, emaciation, polyhidrosis, tremor,polyphagia, frequent defecation, aversion to heat, insomnia with dreaminess, amnesia,lassitude, fatigue, thirst with dry mouth were recorded before and after treatment.Meanwhile, signs such as body weight goiter, cxophthalmos, resting pulse rate, tremor inthe thyroid region, vascular murmur, skin rash were also recorded.Seram levels of thyroid function parameters of TT₃, TT₄, FT₃, FT₄ and thyroidstimulating hormone (TSH) were tested. Levels of thyroglobulin antibodies (TGAb),thyroid pcroxidase antibody (TPO-Ab) were exarnincd by immunology method. Cellapoptosis was evaluated by detecting serum sFas and Bcl-2 levels. The above indexes wereexamined before and after treatment.Routine cxarnination of blood, urine and stool as well as liver and kidney functionwcrc performed once per month, thus to evaluate the toxic and side effects.ResultsAfter treatment for 3 months, 21 patients wcrc clinically effective, 13 markedlyeffective, 6 effective, 0 ineffective, and the total effective rate was 100% in the treatmentgroup; 14 patients.were clinically effective, 13 markedly effective, 7 effective, 6 ineffective,and the total effective rate was 85% in the control group. The effect in the treatment wassuperior to the control group(p＜0.05). For the effect on relieving TCM syndrome, 13patents were clinically cured, 11 markedly effective, 16 effective and 0 ineffective and thetotal effective rate was 100% in the treatment group; 7 patents were clinically cured, 7markedly effective, 25 effective and 1 ineffective and the total effective rate was 97.5% inthe control group; the effect in the treatment group was superior to that in the controlgroup(p＜0.05). The effect on relieving symptom scoring in the treatment group was alsobetter than that in the control group(p＜0.05). The symptom scores in the two groups wereimproved after treatment (p＜0.01 as compared with those before treatment), there existedsignificant difference between the two groups (p＜0.05). The score difference beforeand after treatment in the treatment group was superior to that in the controlgroup (p＜0.05).After treatment, heart rate decreased in the two groups(p＜0. 01 as compared with thatbefore treatment), and the decrease was obvious in the treatment group as compared withthe control group(p＜0.01). The body weight was increased in the two groups after treatment. The difference ofbody weight increase was significant (p＜0.05)in the treatment group before and aftertreatment, but insignificant (p＞0.05)in the control group.After treatment, serum levels of FT₃, FT₄, TT₃ and TT₄ were obviously decreased inthe two groups, TSH was obviously recovered in the treatment group(p＜0.01 as comparedwith those before treatment), and the decrease differences of serum thyroid hormones ofFT₃, FT₄, TT₃, TT₄ and TSH were insignificant (p＞0.05) in the two groups.Thyroglobulin antibody (TGAb) and thyroid peroxidase antibody (TPO-Ab) weredecreased to different degrees in the two groups after treatment(p＜0.01 as compared withthose before treatment), and the decrease was obvious in the treatment group as comparedwith that in the control group(p＜0.01).sFas and Bcl-2 levels were decreased in the two groups after treatment(p＜0.01 ascompared with those before treatment), and the decrease difference was obvious in the twogroups(p＜0.01).During treatment, leukopenia was not found in the treatment group but was found in 2patients of the control group, drug rash was found in 1 of the treatment group and in 4 ofthe control group, hepatic function was damaged in 1 of the treatment group and in 4 of thecontrol group. The side effects were not obvious in the treatment group as compared thosein the control group, indicating that Yingqiling is safe for hyperthyroidism but the sideeffects of methimazole in Yingqiling should be avoided during long-term application.ConclusionThe root of pathogenesis of Graves disease is associated with hyperactive fire due toyin deficiency, i.e., predominance of yang and decline of yin (hyper-proliferation andapoptosis decrease of the body cells). The clinical manifestations of Grave disease arecharacterized as goiter and exophthalmos. Yingqiling has the actions of nourishing yinand clearing heat, activating blood and subsiding swelling, and can promote the recovery ofyin fluid (promoting cell apoptosis),and inhibit the hyperactivity of yang Qi (inhibitinghyper-proliferation) in the treatment of Graves disease. Meanwhile, the herbs in Yingqilingcan induce cell apoptosis. Yingqiling decrease the serum levels of sFas and Bcl-2, thusinduce the cell apoptosis and relieve goiter, inhibit the secretion of thyroid hormone andrelieve the syndrome of yin deficiency and yang hyperactivity. This may be the therapeuticmechanism of Yingqiling in the treatment of Graves disease.Yingqiling has a certain effect for hyperthyroidism(graves disease). It can relieve thesymptoms and signs of goiter and exophthalmos effectively, and has an obvious effect onimmune indexes and cell apoptosis, but has no obvious effect on thyroid hormones levels as compared with the western medicine. Yingqiling, which is composed of herbal medicineand methimazole, has less side effects on blood routine, and liver and kidney function, andit is a safe drug for hyperthyroidism. Yingqiling is worth of wide clinical application.