OBJECTIVE To explore the ameliorative effect of Tiaozhi Xiaoban Mixture on atherosclerosis and the potential role of long non-coding RNA(Linc RNA) in anti-atherosclerosis.

METHODS A model of atherosclerosis was established in SD rats subjected to a high-fat diet. At 4 weeks post-modeling, thoracic aortic tissues from atherosclerotic rats were collected for hematoxylin-eosin (HE) staining to systematically evaluate the anti-atherosclerotic effects of Tiaozhi Xiaoban Mixture at different doses. Biochemical kits were utilized to assess relevant indices related to blood lipid levels as well as liver and kidney function, thereby evaluating the impact of Tiaozhi Xiaoban Mixture on these parameters. Enzyme-linked immunosorbent assay (ELISA) was employed to measure serum inflammation markers influenced by Tiaozhi Xiaoban Mixture. Additionally, TUNEL staining and Western blot analysis were conducted to examine the apoptotic effects of Tiaozhi Xiaoban Mixture on thoracic aorta tissue. Finally, qPCR was used to detect the expression levels of Linc-HC, MALAT1, etc., in order to evaluate how Tiaozhi Xiaoban Mixture affecting these specific RNA molecules.

RESULTS Following treatment with Tiaozhi Xiaoban Mixture, the blood lipid profiles indicated that total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) were significantly down-regulated (P < 0.05, P < 0.01), while high-density lipoprotein cholesterol (HDL-C) levels were up-regulated in the atherosclerotic rats. Moreover, serum levels of liver and kidney function markers such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine (Cr) exhibited down-regulation(P < 0.05, P < 0.01). Additionally, pro-inflammatory factors including interleukin-6 (IL-6), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), and matrix metallopeptidase 9 (MMP-9) were also reduced (P < 0.01), whereas the anti-inflammatory factor interleukin-10 (IL-10) was found to be elevated (P < 0.01). Furthermore, after oral administration of Tiaozhi Xiaoban Mixture, expression levels of apoptosis-related factors NLRP3, ASC, Cleaved Caspase-1, Cleaved IL-1β, Puma, Bax, Noxa, and MDM2 in thoracic aorta tissues from the atherosclerotic rats showed significant down-regulation (P < 0.05, P < 0.01). Notably, following treatment with Tiaozhi Xiaoban Mixture, mRNA levels of Linc-HC decreased while mRNA expression of MALAT1 increased (P < 0.05, P < 0.01).

CONCLUSION Tiaozhi Xiaoban Mixture may inhibit the expression of Linc-HC and up-regulate the expression of MALAT1 to reduce the formation of atherosclerotic plaque, improve abnormal blood lipids and liver and kidney function, alleviate inflammation and inhibit apoptosis.