[Qingxue Xiaozhi Formula ameliorates endothelial inflammation in glucose and lipid metabolism disorders via visceral adipose tissue exosome miR-27b-3p-mediated PPARα/NF-κB signaling pathway].

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This study aimed to explore the mechanism of Qingxue Xiaozhi Formula in ameliorating endothelial inflammation in glucose and lipid metabolism disorders through the visceral adipose tissue exosome miR-27b-3p-mediated peroxisome proliferator-activated receptor α(PPARα)/nuclear factor-kappa B(NF-κB) signaling pathway. A Zucker diabetic fatty(ZDF) rat model was induced by Purina 5008 feed, and inflammation models of adipocytes and human umbilical vein endothelial cells(HUVECs) were induced by glucose combined with oxidized low-density lipoprotein(ox-LDL). ZDF rats were randomly allocated into model, low-dose Qingxue Xiaozhi Formula, high-dose Qingxue Xiaozhi Formula, and metformin groups, with Zucker lean(ZL) rats serving as the normal group. After 7 weeks of drug intervention, the body weight, Lee's index, fasting blood glucose, oral glucose tolerance, serum lipid levels, and liver enzyme levels were measured. Hepatic pathological changes were observed via hematoxylin-eosin(HE) and oil red O staining. miRNAs sequencing was used to quantify the expression of miRNAs in exosomes derived from the visceral adipose tissue. Immunofluorescence staining was employed to detect aortic vascular cell adhesion molecule-1(VCAM-1) expression. The cell counting kit-8(CCK-8) method was adopted to examine cell viability. qRT-PCR, enzyme-linked immunosorbent assay(ELISA), and Western blot were employed to measure the mRNA and protein levels of miR-27b-3p, PPARα, NF-κB p65, VCAM-1, and interleukin-6(IL-6). The results showed that compared with the model group, Qingxue Xiaozhi Formula reduced Lee's index, fasting blood glucose, serum lipid levels, and liver enzyme levels in ZDF rats(P<0.05), improved oral glucose tolerance and the expression profile of miRNAs in exosomes derived from the visceral adipose tissue, and alleviated hepatic lipid deposition and aortic endothelial inflammation. In cell experiments, Qingxue Xiaozhi Formula increased the viability of HUVECs and adipocytes, downregulated the mRNA and protein levels of miR-27b-3p, NF-κB p65, VCAM-1, and IL-6 in endothelial cells, and upregulated the mRNA and protein levels of PPARα(P<0.05). These effects could be mimicked by treatment with an miR-27b-3p antagonist or exosome synthesis/release inhibitors. The results indicate that Qingxue Xiaozhi Formula can alleviate endothelial inflammation and vascular complications in glucose and lipid metabolism disorders by regulating visceral adipose tissue exosome miR-27b-3p, activating PPARα, and inhibiting the NF-κB signaling pathway.

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