Effect of electroacupuncture on Nrf2/NLRP3/Caspase-1 pathway mediated-pyroptosis in mice with Parkinson's disease. / ç”µé’ˆå¯¹å¸•é‡‘æ£®ç— å°é¼ Nrf2/NLRP3/Caspase-1通路介导的细胞焦亡的影响.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on nuclear transcription factor E2 related factor 2 (Nrf2)/NOD-like receptor family pyrin domain-containing protein 3 (NLRP3)/cysteine aspartic acid specific protease-1 (Caspase-1) pathway in the substantia nigra (SN) of mice with Parkinson's disease (PD), so as to explore the neuroprotective mechanism of EA. METHODS: Forty C57BL/6 male mice were randomly divided into 4 groups, namely, control, PD model, EA and sham-EA groups, with 10 mice in each group. The PD mouse model was established by gavage of rotenone for 4 weeks. Mice in the EA group were given EA stimulation (1 mA, 2 Hz) at "Fengfu" (GV36), bilateral "Taichong" (LR3) and "Zusanli" (ST36) for 30 min, once daily for 2 consecutive weeks. And mice in the sham-EA group were given acupuncture at the subcutaneous areas of the same acupoints without EA stimulation. The open-field test was used for assessment of mouse behavior. The levels of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in the serum were detected by enzyme-linked immunosorbent assay . The positive expression of tyrosine hydroxylase (TH) in SN was determined by immunohistochemistry. The mRNA expression levels of Nrf2, NLRP3, Caspase-1, gasdermin D(GSDMD), IL-1ß, IL-18 and the protein expression levels of Nrf2, NLRP3, Caspase-1 and GSDMD in the SN were detected by quantitative real-time PCR and Western blot, separately. RESULTS: After modeling, compared with the control group, the behavioral score was increased (P<0.01), the total exercise time, the total distance and the average speed were decreased (P<0.01), and the positive expression of TH and the mRNA and protein expression levels of Nrf2 in the SN were decreased (P<0.01), while the contents of IL-1ß and IL-18 in serum, the mRNA and protein expression levels of NLRP3, Caspase-1 and GSDMD and the mRNA expression levels of IL-1ß and IL-18 in the SN were up-regulated (P<0.01) in the PD model group. Following EA intervention, the behavioral score was decreased(P<0.01), the total exercise time, total distance and average speed were increased (P<0.01), the positive expression of TH and the mRNA and protein expressions of Nrf2 in SN were up-regulated (P<0.01, P<0.05), while the contents of IL-1ß and IL-18 in serum, the mRNA and protein expression levels of NLRP3, Caspase-1 and GSDMD as well as the mRNA expression levels of IL-1ß and IL-18 in the SN were down-regulated (P<0.01, P<0.05) in the EA group relative to the PD model and sham-EA groups. There were no significant differences in the above indicators between the PD model and sham-EA groups. CONCLUSIONS: EA stimulation of GV36, LR3 and ST36 can improve motor deficits, reduce the loss of dopamine neurons in the SN, and inhibit neuroinflammatory responses in mice with PD, which may be related to its effects in regulating the Nrf2/NLRP3/Caspase-1 pathway mediated pyroptosis.

Effects of electroacupuncture on the intestinal thioredoxin interaction protein/Nod-like receptor 3 signaling pathway in mice with Parkinson's disease. / ç”µé’ˆå¯¹å¸•é‡‘æ£®ç— å°é¼ è‚ é“ç¡«æ°§è¿˜è›‹ç™½äº’ä½œè›‹ç™½/NODæ ·å—ä½“3信号通路的影响.

OBJECTIVES: To observe the effects of electroacupuncture (EA) at "Fengfu" (GV16), "Taichong" (LR3) and "Zusanli" (ST36) on α-synuclein (α-syn), Occludin, Claudin-1, thioredoxin interaction protein (TXNIP) and Nod-like receptor 3 (NLRP3) in Parkinson's disease (PD) mice, so as to investigate the mechanisms of EA on intestinal barrier function and inflammation in PD mice. METHODS: Thirty six C57BL/6 mice were randomly divided into control, model and EA groups, with 12 mice in each group. PD mice model was induced by rotenone intragastric administration for 28 days. Mice in the EA group were treated with EA (2 Hz, 1 mA) at GV16, LR3 and ST36 for 30 min, once a day for 14 days. The behavioral scores were observed. The total distance of autonomic movement was measured by open field test. The expression level of α-syn in substantia nigra and colon tissue was determined by immunohistochemistry. The colonic morphology and goblet cell distribution were observed by Alcian blue staining. The expression levels of Occludin, Claudin-1, TXNIP and NLRP3 mRNA in colon tissue were detected by real-time fluorescence quantitative PCR. RESULTS: Compared with the control group, the behavioral scores of rats were increased (P<0.01)；the total distance of autonomous movement was decreased (P<0.01)；the positive expression level of α-syn in the substantia nigra and colon was increased (P<0.01)；the goblet cells and crypts in colon tissue were reduced, and the muscular layer was thinner；the expression levels of Occludin and Claudin-1 mRNAs in colon tissue were decreased (P<0.01) while TXNIP and NLRP3 mRNAs were increased (P<0.01) in the model group. Compared with the model group, the surface villi of colon tissue was more complete, the goblet cells and crypts were increased, and the muscular layer was thickened；the other indexes were reversed (P<0.01, P<0.05) in the EA group. CONCLUSIONS: EA at GV16, LR3 and ST36 can reduce the abnormal accumulation of α-syn in the substania nigra and colon tissue of PD mice, alleviate the damage of intestinal barrier, regulate TXNIP/NLRP3 signaling pathway, so as to delay the occurrence and development of PD.