1.Study on Efficacy and Preliminary Mechanism of Qinggan Sanjie Xiaoying Decoction in the Treatment of Hashimoto's Thyroiditis
Xin'ai LI ; Zhiguo DING ; Xiaoheng CHEN ; Zhe LI ; Shuo QI
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(2):154-159
Objective To explore the clinical efficacy and mechanism of Qinggan Sanjie Xiaoying Decoction in the treatment of Hashimoto's thyroiditis with syndrome of stagnation heat of liver meridian and stagnation of spleen deficiency and phlegm.Methods Totally 70 patients were divided into control group and medicine group according to their wishes,with 35 patients in each group.Both groups were restricted to an iodine diet.The medicine group was given Qinggan Sanjie Xiaoying Granules,1 sachet at a time,twice a day,orally.The treatment for both groups lasted for 4 weeks.20 healthy people were chosen as the healthy group.The clinical efficacy of both groups was observed.TCM symptom score,thyroid antibody titer levels(TPOAb,TGAb),changes in thyroid volume and isthmus of both groups before and after treatment were compared.Levels of serum IKKα,IKBα and TNF-α of the three groups were compared.Adverse reactions of patients daring the treatment period were monitored.Results The total effective rate of the medicine group was 85.71%(30/35),while the control group was 20.00%(7/35).The medicine group was superior to the control group(P<0.05).Compared with before treatment,the medication group showed significant improvement in TCM symptom scores,TPOAb and TGAb titer levels,thyroid volume,and thyroid isthmus thickness after treatment(P<0.05).After treatment,TCM symptom score,thyroid volume in the medicine group were lower than those in the control group(P<0.05),and the decrease rate of TPOAb titer was higher than that in the group(P<0.05).The levels of IKKα and TNF-α before treatment of medicine group and control group were higher than that in the healthy control group,and the level of IKBα was lower than that of the healthy control group(P<0.05);compared with before treatment,the levels of IKKα and TNF-α in the medicine group decreased,and the level of IKBα increased(P<0.05);after treatment,the levels of IKKα and TNF-α in the medicine group were lower than that in the control group,and IKBα was higher than the control group(P<0.05).No adverse events were observed during the treatment period in both groups of patients.Conclusion Qinggan Sanjie Xiaoying Decoction can reduce the antibody titer level,thyroid enlargement,isthmus thickness,and TCM syndrome score in the treatment of Hashimoto's thyroiditis.It is safe and effective in clinical practice.Qinggan Sanjie Xiaoying Decoction may play a therapeutic role by interfering with NF-κB signaling pathway.
2.The clinical study of internal and external combined treatment of HT by Professor Ding Zhiguo based on "dimple corresponding theory"
Xin'ai LI ; Shuo QI ; Xiaoheng CHEN ; Zhe LI ; Zhiguo DING
International Journal of Traditional Chinese Medicine 2024;46(5):580-587
Objective:To evaluate the clinical efficacy of Professor Ding Zhiguo's internal and external combined treatment of Hashimoto's disease, and to explore its mechanism.Methods:Prospective cohort study. A total of 85 patients of professor Ding Zhiguo from Sun Simmiao Hospital of Beijing University of Chinese Medicine and Dongzhimen Hospital of Beijing University of Chinese Medicine from August 2022 to March 2023 were selected and divided into control group (43 cases) and drug group (42 cases) by random number table method. Another 20 healthy volunteers were recruited for health control observation. The control group was given iodine restricted diet, the drug group was treated with Qinggan Sanjie Xiaoying Prescription combined with Liqi Sanjie Xiaoying Ointment, and the healthy control group was not treated with any intervention. Both drug group and control group were observed continuously for 4 weeks. TCM syndrome scores were performed before and after treatment. Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) were used to assess the degree of anxiety and depression, Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality, and fatigue severity Scale (FSS) was used to assess the degree of fatigue. Lower limb lymphedema self-sensory symptoms assessment questionnaire was used to evaluate the symptoms of lower limb lymphedema. The serum levels of thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) were measured by automatic electrochemiluminescence immunoassay, and the reduction rate was calculated. The levels of serum Akt, ERK and protein kinase C (PKC) were detected by ELISA. The thyroid volume was calculated and the anterior and posterior diameter of the isthmus was recorded. The clinical efficacy and safety were evaluated.Results:The total effective rate was 71.43% (30/42) in the drug group and 27.91% (12/43) in the control group, with statistical significance ( χ2=16.10, P<0.01). The serum TPOAb [137.95 (141.44) IU/ml vs. 153.40 (154.93) IU/ml, Z=-4.37] and TGAb [182.00 (238.52) IU/ml vs. 190.50 (257.55) IU/ml, Z=-2.13] levels in the drug group were lower after treatment ( P<0.01 or P<0.05), and the decrease rate of TPOAb [15.62 (21.90)% vs. -6.42 (32.89)%, Z=-4.12] and TGAb [5.25 (20.49)% vs. -0.72 (17.67)%, Z=-2.67] were higher than that in the control group ( P<0.01). The thyroid volume [11.37 (6.48) cm 3vs. 12.89 (6.63) cm 3, Z=-2.95] and isthmus thickness [0.27 (0.14) cm vs. 0.28 (0.15) cm, Z=-2.18] in the drug group were reduced after treatment compared with that before treatment ( P<0.05). TCM syndrome scores (6.10±1.38 vs. 14.42±7.35, t=-7.29), HAMA (5.21±1.32 vs. 9.28±2.25, Z=-7.02), HAMD (8.28±3.17 vs. 10.42±5.28, t=-2.26), PSQI (6.00±2.16 vs. 9.47±3.08, t=-6.01), FSS (34.71±5.51 vs. 38.23±8.35, t=-2.30), lower limb lymphedema self-induced symptom evaluation questionnaire scores (4.95±2.56 vs. 7.86±3.07, t=-4.74) after treatment were lower than before treatment and lower than control group ( P<0.001 or P<0.05).The serum levels of Akt [52.28 (17.72) μmol/L vs. 44.38 (2.75) μmol/L],ERK [2 843.43 (607.90) ng/L vs. 2 648.25 (290.74) ng/L],PKC [8.87 (3.10) pmol/L vs. 7.88 (1.25) pmol/L] in drug group were higher than those in the healthy control group before treatment ( P<0.05), the levels of Akt [37.37 (7.90) μmol/L vs. 44.38 (2.75) μmol/L], ERK [2 432.74 (402.56) ng/L vs. 2 648.25 (290.74) ng/L] in drug group were lower than those in the healthy group after treatment ( P<0.05). After treatment, the levels of Akt [37.37 (7.90) μmol/L vs. 52.28 (17.72) μmol/L, 49.56 (9.12) μmol/L], ERK [2 432.74 (402.56) ng/L vs. 2 843.43 (607.90) ng/L, 3 021.76 (360.22) ng/L], PKC [7.37 (1.84) pmol/L vs. 8.87 (3.10) pmol/L, 10.00 (2.42) pmol/L] in drug group were lower than before treatment and lower than control group ( P<0.01). There were no adverse events during treatment in both groups. Conclusion:The internal and external treatment of Hashimoto's disease by Professor Ding Zhiguo can effectively reduce the level of thyroid antibody titer, reduce the thyroid swelling and isthmus thickness, improve the clinical symptoms of patients with Hashimoto's disease, and may play a therapeutic role by interfering with MAPK signaling pathway.
3.Effect of Modified Zhenwutang on Interstitial Fibrosis in Rats with Chronic Renal Failure Based on IL-6/MMP-9/COL-Ⅳ Signaling Pathway
Wanzhe LI ; Yuanyuan ZHANG ; Peipei JIN ; Xin'ai WANG ; Dengzhou GUO
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(16):114-122
ObjectiveTo observe the modulatory effect of modified Zhenwutang on the interleukin-6 (IL-6), matrix metallopeptidase-9(MMP-9), type Ⅳ collagen(COL-Ⅳ) in rats with chronic renal failure (CRF) and to investigate the potential mechanism of its treatment of CRF. MethodFifty male SD rats were randomly divided into a modeling group of 40 rats and a normal group of 10 rats, and the modeling group was prepared by continuous adenine gavage for 12 weeks. After successful modelling, the modelling group was divided into the model group, the low dose (7.2 g·kg-1·d-1) group, the medium dose (14.4 g·kg-1·d-1) group, the high dose (28.8 g·kg-1·d-1) group and the Benadryl hydrochloride (10 mg·kg-1·d-1) group for gavage according to the random number table method, In the normal group and the model group, equal volume of distilled water was administered by gavage for 4 weeks. After the administration, the levels of blood creatinine (SCr), blood urea nitrogen (BUN) and 24 h urine protein (24 h-UTP) were measured, the levels of serum IL-6 were measured by enzyme linked immunosorbent assay(ELISA). Immunohistochemistry (IHC) was used to detect intercellular cell adhesion molecule-1 (ICAM-1), IL-6, MMP-9, and other molecules in the rat kidney. The expression of ICAM-1 mRNA, IL-6 mRNA, MMP-9 mRNA and COL-Ⅳ mRNA in rat kidney tissues was measured by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The expression levels of ICAM-1, IL-6, MMP-9 and COL-Ⅳ in rat kidney tissues were measured by Western blot. ResultCompared with the normal group, the levels of SCr, BUN and 24 h-UTP were significantly increased in the model group (P<0.01); the serum IL-6 level was significantly increased (P<0.01), the tubular lumen was dilated with atrophy, the tubular epithelial cells were necrotic, swollen and vacuolated, the interstitium was infiltrated by a large number of inflammatory cells and collagen fibers were deposited, the levels of IL-6, ICAM-1 and COL-Ⅳ were strongly positive in the tubular interstitium of the model group (P<0.01), The levels of ICAM-1 mRNA, IL-6 mRNA and COL-Ⅳ mRNA were significantly increased (P<0.01) and MMP-9 mRNA was significantly decreased (P<0.05) in the model rats. ICAM-1, IL-6 and COL-Ⅳ protein expression was significantly increased (P<0.01) and MMP-9 protein expression was significantly increased (P<0.01) in the renal tissue, and MMP-9 protein expression was significantly decreased (P<0.01). Compared with the model group, the 24 h-UTP, SCr and BUN levels of rats were significantly reduced after treatment with modified Zhenwutang (P<0.01), the serum IL-6 level was significantly decreased (P<0.01), the renal lesions of rats were significantly improved and collagen fiber deposition was reduced; the expression of IL-6, ICAM-1 and COL-Ⅳ in renal tubules and interstitium was weakened, and MMP-9 in ICAM-1 mRNA, IL-6 mRNA and COL-Ⅳ mRNA levels were significantly reduced (P<0.01) and MMP-9 mRNA levels were significantly increased (P<0.05), ICAM-1, IL-6 and COL-Ⅳ protein expression was significantly reduced (P<0.01) and MMP-9 protein expression was significantly The expression of ICAM-1, IL-6 and COL-Ⅳ proteins was significantly decreased (P<0.01) and MMP-9 protein expression was significantly increased (P<0.01). ConclusionModified Zhenwutang may regulate the IL-6/MMP-9/COL-Ⅳ signaling pathway, thereby reducing proteinuria, improving renal function, reducing renal pathological damage and delaying the progression of CRF interstitial fibrosis.