ABSTRACT
Objective:To evaluate the clinical efficacy of self-made Tingchan Decoction combined with dopasizin tablets in the treatment of Parkinson disease (PD) in the middle and early stages of yin deficiency and wind movement syndrome.Methods:From January 2020 to March 2021, 84 patients with early-stage PD in Weifang Hospital of Traditional Chinese Medicine in Shandong Province who met the inclusion criteria were divided into 2 groups according to the random number table method, with 42 in each group. The control group was given oral dopasehydrazine tablets, and the observation group and the control group were additionally given the self-made Tingchan Decoction. Both groups were treated for 8 weeks. TCM syndrome scores were performed before and after treatment, and the Unified Parkinson Disease Rating Scale (UPDRS) was used to evaluate the severity of PD. The ELISA was used to determine serum homocysteine (Hcy), high mobility the levels of group protein-1 (HMGB1), IL-6, IL-2, substance P and dopamine (DA). The levels of glutamate (Glu) and γ-aminobutyric acid (GABA) were detected by HPLC. The OD value was determined by photometer, and the relative expression levels of microRNA-124 (miR-124) and microRNA-425 (miR-425) were calculated by the 2 -??Ct method to evaluate the clinical efficacy. Results:The total effective rate was 88.1% (37/42) in the observation group and 73.8% (31/42) in the control group, and the difference between the two groups was statistically significant ( Z=-2.56, P=0.011). after treatment, the action score, tremor score, upper limb coordination score and gait score in the observation group were significantly lower than those in the control group ( t values were 7.23, 5.80, 4.25, 4.17, 15.00,respectively, all Ps<0.01). After treatment, the levels of serum Hcy, HMGB1, IL-6 and IL-2 in the observation group were significantly lower than those in the control group ( t values were 12.16, 10.67, 23.11, 9.95, respectively, all Ps<0.01), serum Glu [(71.28±6.46) μmol/L vs. (56.91±5.87) μmol/L, t=10.67], GABA [(292.39±15.46) μmol/L vs. (248.51±14.38) μmol/L, t=13.47] levels in the observation group were significantly higher than those in he control group ( P<0.01); the level of serum substance P [(3.54±0.43) mg/L vs. (5.61±0.52) mg/L, t=19.88] was significantly lower than that of the control group ( P<0.01). The DA [(79.24±0.52) ng/L vs. (70.15±5.36) ng/L, t=7.93] and miR-124 [(4.57±0.74) vs. (2.81±0.47), t=13.01], miR-425 [(3.94±0.83) vs. (2.73±0.97), t=6.14] expression in the observation group were significantly higher than those in the control group ( P<0.01). Conclusion:Self-made Tingchan Decoction combined with dobasilazine can increase the relative expression of miR-124 and miR-425 in the serum of PD patients, promote the release of dopamine, reduce the oxidative stress in the brain, reduce the level of serum inflammatory cytokines, improve the Symptoms, and protect nerve cells.
ABSTRACT
This study explores the regulatory effect of astragaloside Ⅳ on miR-17-5 p and its downstream proprotein convertase subtillisin/kexin type 9(PCSK9)/very low density lipoprotein receptor(VLDLR) signal pathway, aiming at elucidating the mechanism of astragaloside Ⅳ against atherosclerosis(AS). In cell experiment, oxidized low-density lipoprotein(ox-LDL) was used for endothelial cell injury modeling with vascular smooth muscle cells(VSMCs). Then cells were classified into the model group, miR-17-5 p inhibitor group, blank serum group, and astragaloside Ⅳ-containing serum group based on the invention. Afterward, cell viability and the expression of miR-17-5 p, VLDLR, and PCSK9 mRNA and protein in cells in each group were detected. In animal experiment, 15 C57 BL/6 mice were used as the control group, and 45 ApoE~(-/-) mice were classified into the model group, miR-17-5 p inhibitor group, and astragaloside Ⅳ group, with 15 mice in each group. After 8 weeks of intervention, the peripheral serum levels of interleukin-6(IL-6), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α), and the expression of miR-17-5 p, VLDLR, and PCSK9 mRNA in the aorta of mice were detected. The pathological changes of mice in each group were observed. According to the cell experiment, VSMC viability in the miR-17-5 p inhibitor group and the astragaloside Ⅳ-containing serum group was higher than that in the model group(P<0.05). The mRNA and protein expression of miR-17-5 p and VLDLR in VSMCs in the miR-17-5 p inhibitor group and the astragaloside Ⅳ-containing serum group was lower than that in the model group(P<0.05), but the mRNA and protein expression of PCSK9 was higher than that in the model group(P<0.05). As for the animal experiment, the levels of IL-6 and TNF-α in the peripheral serum of the miR-17-5 p inhibitor group and the astragaloside Ⅳ group were lower(P<0.05) and the serum level of IL-10 was higher(P<0.05) than that of the model group. The mRNA expression of miR-17-5 p and VLDLR in the aorta in the miR-17-5 p inhibitor group and the astragaloside Ⅳ group was lower(P<0.05), and PCSK9 mRNA expression was higher(P<0.05) than that in the model group. Pathological observation showed mild AS in the miR-17-5 p inhibitor group and the astragaloside Ⅳ group. In summary, astragaloside Ⅳ can prevent the occurrence and development of AS. The mechanism is that it performs targeted regulation of miR-17-5 p, further affecting the PCSK9/VLDLR signal pathway, inhibiting vascular inflammation, and thus alleviating endothelial cell injury.