OBJECTIVES: To investigate the regulatory role of the NLRP3 signaling pathway in hepatocyte pyroptosis in nonalcoholic steatohepatitis (NASH) under hypoxia. METHODS: Twenty-four male C57BL/6 mice were randomized equally into hypoxic control (A), hypoxic NASH model (B), hypoxic NASH+NLRP3 inhibitor (C), and hypoxic NASH+caspase-1 inhibitor (D) groups. In groups B-D, the mice were fed a methionine choline-deficient (MCD) diet under hypoxic conditions (to simulate a 5000 m altitude) for 6 weeks; the mice in groups C and D received intraperitoneal injections of the respective inhibitors every other day. RESULTS: Compared with those in group A, the mice in group B showed significantly elevated serum levels of FBG, TC, TG, ALT and AST, increased liver lipid content, inflammatory cell infiltration and collagen fiber deposition, and enhanced hepatic expressions of NLRP3, caspase-1, IL-1β and GSDMD proteins, with obvious swelling, cristae breakage, vacuolization, and outer membrane disruption of the mitochondria, ribosome loss in the cytoplasm, destruction of the nuclear membrane, and pathological changes of the rough endoplasmic reticulum. Treatment with NLRP3 inhibitor and caspase-1 inhibitor both significantly lowered serum levels of TC, TG, ALT and AST (but without significantly affecting FBG) in the mouse models, and reduced liver lipid content, inflammatory cell infiltration, collagen deposition, and expression levels of NLRP3, caspase-1, GSDMD and IL-1β. The treatments also significantly improved pathological changes in the mitochondria, ribosomes and endoplasmic reticulum in liver tissues of the mice. CONCLUSIONS NLRP3 signaling pathway plays a key role in promoting hepatocyte pyroptosis in NASH mice under hypoxic condition, and inhibiting this pathway can effectively reduce liver inflammation, suggesting its potential as a therapeutic target for NASH treatment.
Animals ; Non-alcoholic Fatty Liver Disease/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Pyroptosis ; Mice, Inbred C57BL ; Male ; Hepatocytes/pathology* ; Signal Transduction ; Mice ; Hypoxia/metabolism* ; Caspase 1/metabolism* ; Interleukin-1beta/metabolism* ; Liver/metabolism*

Objective Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)and network pharmacology technology combined with pharmacodynamic experiments were used to analyze the quality markers(Q-markers)in Saorilao Qingfei Zhike Capsules.Methods Using UPLC-Q-TOF-MS technology,the chemical components in different polar extracts of Saorilao Qingfei Zhike Capsules was analyzed.Potential pharmacological components were screened by using antitussive and expectorant models.The"components-targets-diseases"network was constructed and potential Q-markers were screened by network pharmacology technology.Then we conducted pharmacodynamic validation to confirm the Q-markers,which have antitussive and expectorant effects in Saorilao Qingfei Zhike Capsules.Results A total of 120 compounds were obtained from the Saorilao Qingfei Zhike Capsules through qualitative analysis.Among the extracts of different polarity,44 compounds were derived from petroleum ether extract,85 compounds were derived from ethyl acetate extract,79 compounds were derived from n-butanol extract,and 71 compounds were derived from water extract.The results of pharmacological experiments showed that among extracts of different polarity,petroleum ether extract had the best antitussive effect,while n-butanol extract had the best expectorant effect.Three core components for eliminating phlegm and relieving cough were screened through network pharmacology techniques:farcalinol,farcalinediol,and rubimaillin.Pharmacodynamic studies verified that all core components mentioned above have certain antitussive and expectorant effects.Conclusion Based on the above research,farcalinol,farcalindiol,and rubimaillin can be used as Q-markers for the antitussive and expectorant effects of Saorilao Qingfei Zhike Capsules.This paper provides reference for the quality standard of Saorilao Qingfei Zhike Capsules.

Objective:To explore the effect of traditional Chinese medicine fumigation and washing on the clinical indicators of elderly patients with distal radius fractures after small splint fixation.Methods:From November 2015 to November 2018, 180 elderly patients with fracture of the distal radius in Ningbo Hospital of Traditional Chinese Medicine were selected, and they were divided into control group and observation group according to the random digital table method, with 90 cases in each group.The two groups were given manual reduction and small splint fixation treatment, and the observation group was treated with traditional Chinese medicine fumigation on the basis of the control group therapy.The related inflammatory cytokines in patients plasma and serum viscosity(TNF-α, IL-1, IL-6) were detected, and the clinical curative effect and adverse reactions were observed.Results:Before treatment, there were no statistically significant differences in plasma viscosity and blood inflammatory factors(TNF-α, IL-1, IL-6) between the two groups( t=-0.171, -0.126, 0.483, 0.459, all P>0.05). After treatment, the above indicators in the two groups were significantly lower than those before treatment(observation group: t=38.970, 14.684, 72.258, 53.612; control group: t=20.098, 19.045, 33.962, 34.822, all P<0.05), which in the observation group were lower than those in the control group ( t=-30.239, -7.043, -31.815, -10.359, all P<0.05). The total effective rate of the observation group was 88.88%(80/90), which was higher than 71.11%(64/90) of the control group, the difference was statistically significant between the two groups(χ2=8.889, P<0.05). Conclusion:For the elderly patients with distal radius fracture, the combination of reduction and small splint fixation and fumigation with traditional Chinese medicine can significantly improve the hemorheology of the patients and reduce the contents of inflammatory factors in the body, with significant efficacy and no adverse reactions, which is worthy of clinical application.