Effect Of Qingyangtoujie Therapy On Th1/Th2 Cell Imbalance And Vascular Damage In Yin-deficient SLE Patients

Objectives:Focusing on the imbalance of immunity in SLE, the study was to investigate the imbalance of Th1 and Th2 cell immunity as well as vascular damage factors in the pathological process of SLE. Clinical experiments were carried out to explore the effect of Qingyangtou jie therapy used to treat SLE.Methods:1,Clinical trial:Prospective a single blind Randomized Controlled trial was adopted, and 42 cases were divided into treatment group (22 cases) and control group (20 cases). We selected 12 persons as a normal group in Addition. The patients in treatment group were treated with a therapy with Qing-yang-tou-jie mixture and western medicine, while those in control group were treated with placebo and western medicine. The patients' condition activity scores, main symptom scores, TCM syndrome scores and side effects of cortin were evaluated after 6 month of treatment. TH1 cell factors (IFN-γ, IL-12), TH2 cell factors (IL-10, IL-4) and vascular injury factors (sTM, vWF) in serum were tested by ELISA simultaneously.2,Animal experiment:Twenty-four female MRL/lpr mice of 8 to10 weeks were divided into therapentic group, western medicine treatment group, combined Chinese and western medicine treatment group and model control group. Six female BALB/C mice of 8 to 10 weeks were selected as a normal group. After continuous exposure therapy of six weeks, TH1 cell factors (IFN-γ, IL-12), TH2 cell factors (IL-10, IL-4) and vascular injury factors (sTM, vWF) in serum were tested; renal pathological changes and ultrastructure were observed by light microscopy and electronic microscopy. Result1,Clinical trial:Thirty-eight cases in the clinical trial were recorded completely, which involves 20 treatment cases,18 control cases and 12 normal control cases. There was no difference in sex and age of these cases. There was no difference in the case lost rate, disease progress between therapentic and control groups. (1)Clinical effects:After 6 month of treatment, the patients'condition activity score, main symptom score, TCM syndrome score and diversity of prednisone dosage were significantly ameliorated than those of pre-treatment. The improvement in the condition of treatment group was significantly superior to the control group (P<0.01).(2) Influence on cell factors:Before treatment, compared with normal group, the factors such as IL-12, IFN-γ, IL-10 and IL-4 in SLE patients increased obviously (p<0.05), and IL-12/IL-10, IFN-γ/IL-4 decreased significantly (P <0.01). Vascular injury factors also decreased significantly. After 6 month of treatment, the serous cell factors (both Thl and Th2 cell factors) decreased significantly in the treatment group, and vascular injury factor (sTM, vWF) decreased too. At the same time, Th1/Th2 ratio (both IFN-γ/IL-4 and IL-12/IL-10) in the treatment group increased, the difference was significant.(3) Compared with control group, the treatment group had reduced incidences of side effects, such as Cushing syndrome, hypertension, peptic ulcer, alopecia, secondary leucopenia and liver dysfunction, and the differences were extraordinary remarkable (P<0.01)2,Animal experiment:(1)Th1 cell factors:No significant differences in IL-12 level were found in these five groups, independently (p>0.05), but there was significant difference in IFN-γbetween MRL/lpr mice and BALB/C mice (p<0.05);(2)Th2 cell factors:Compared with normal group, the model mice's serous level of IL-10 and IL-4 increased significantly (p<0.05). While the level of Th2 cell factors (IL-10, IL-4) decreased significantly in the therapentic group and the combined Chinese and western medicine treatment group. The serous level of IL-4 decreased in western medicine group.(3)Th1/Th2 balance:The ratio of Th1/Th2 (both IL-12/IL-10 and IFN-γ/IL-4) decreased in all groups except the normal group. But the ratio of IFN-γ/IL-4 was increased significantly in the therapic group, the western medicine group and the with group combined Chinese and western medicine. The serous level of IL-12/IL-10 was effectively increased in Chinese and western medicine group (p<0.05);(4)Vascular injury factor:The serous vWF and sTM increased greatly in model mice (MRL/lpr mice). The therapentic treatment and the combined Chinese and western medicine treatment lowed greatly both vWF and sTM in the model mice. Western medicine treatment lowered the level of serous vWF in model mice.(5)Renal Pathology:Under microscope, glomerulus proliferation or atrophy were found by observing renal pathological sections. There were also capillo fibrinoid necrosis and chronic inflammatory cells infiltrated around blood vessels. Under electron microscope, incrassation of basilar membrane, swollen endothelial cells, and dense deposits near basilar membrane were observed. All the treatments might relieve the micro pathology to some extent.Conclusion1. According to the result of clinical experiment, the balance of Th1/Th2 was disturbed in SLE patients, with the rise of Th2 and increase in the expression of vWF and STM in the serum. Qing-yang-tou-jie as the principal treatment in combination with western medicine was effective to reduce symptoms of SLE and Yin-deficiency, and the effect was superior to that of west medicine alone. The combined therapy was effective to improve the balance between Th1/Th2 cells, reduce the expression of vWF and sTM in the surum, relieve the vascular injury, and reduce the dosage of prednisone as well as its toxic side effects.2. Experiment on animal showed that MRL/lpr mice suffered disturbance in Th1/Th2 balance, which was reflected by increase of Th2, decrease in Th1/Th2, increased expression of vWF and sTM in the serum, and pathologic changes in the kidney tissue. Qing-yang-tou-jie therapy was able to decrease the expression of Th2, increase IFN-γ/IL-4 ratio, suppress the expression of vWF and sTM in the serum and relieve pathological changes of kidney.3. There was difference in the results of the animal experiment and clinical experiments. The Th1 cell factors in MRL/Lpr mice were lower or had no difference compared with the normal control mice, while in SLE patients, serum Th1 factors were significantly higher than in the control group. The difference in the results between the model mice and SLE patients might be due to difference in disease mechanisms.4 Qing-yang-tou-jie therapy effectively to ameliorate the imbalance of Th1/Th2 cell factors, and thus helped to maintain the normal function of T cells, suppress the abnormal reproduction of B cells, reduce the inflammatory injury caused by the deposition of inflammatory factors and immune complex, and protect vascular endothelium, achieving the effect to cure SLE.