OBJECTIVE To explore the effect of Huangqin decoction on improving peritubular fat inflammatory microenvironment and protecting vascular endothelial function in obese hypertensive rats by regulating the NEK7-NLRP3/IL-1β inflammatory axis.
METHODS Fifty 4-week-old male Wistar rats were selected, 10 of which were randomly selected as the control group, and the other 40 were fed a high-salt and high-fat diet to establish an obese hypertension model. The rats with successful modeling (20 rats) were randomly divided into the model group, normal-dose Huangqin decoction group, high-dose Huangqin decoction group, and IL-1β inhibitor group, with 5 rats in each group. From the 12th week, the normal-dose group was gavaged with Huangqin decoction 2.835 g ·kg-1, the high-dose group was gavaged with Huangqin decoction 5.67 g ·kg-1, and the IL-1β inhibitor group was intraperitoneally injected with 1.5 mg ·kg-1 AS101, 3 times a week, for 8 weeks. The rats were weighed and blood was collected 12 h after the last administration, and the thoracic aorta and perivascular fat tissue were isolated. Serum inflammatory factors were detected, pathological changes were observed, eNOS expression was detected by immunofluorescence, and NEK7, NLRP3, Caspase-1, ASC, and IL-1β expression levels were detected by Western blot and qPCR.
RESULTS The rats in the model group had a significant increase in body weight, an increase in the area of peritubular fat lipid droplets, and severe endothelial injury; systolic blood pressure, diastolic blood pressure, serum IL-1β, IL-6, and TNF-α were significantly elevated in the model group, and the expression of eNOS was significantly reduced, and the expression levels of NEK7, NLRP3, Caspase-1, ASC, and IL-1β proteins and mRNAs were significantly elevated. Compared with the model group, rats in the Huangqin decoction and IL-1β inhibitor groups had lower body weights, reduced endothelial damage, lower systolic and diastolic blood pressures, lower serum IL-1β, IL-6, and TNF-α, and higher eNOS expression. NEK7, NLRP3, Caspase-1, ASC and IL-1β protein expression was significantly reduced in the high dose group of Huangqin decoction and the IL-1β inhibitor group. In addition, Huangqin decoction protected the endothelial function of obese hypertensive vessels in a dose-dependent manner, with the effect being more pronounced in the high-dose group.
CONCLUSION Huangqin decoction can improve the inflammatory microenvironment of perivascular fat and protect the vascular endothelial function in obese hypertension by regulating the NEK7-NLRP3/IL-1β inflammatory axis.
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