·The SD rat model of NAFLD was established. Rats were randomly divided into 4 groups: control group, model group (high fat), shRNA-negative control (NC) interference model group (high fat+shRNA-NC) and Pcsk9-shRNA interference model group (high fat+ Pcsk9-shRNA). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect Pcsk9 gene interference efficiency. Fasting serum insulin was determined by radioimmunoassay. Automatic biochemical analyzer was used to detect levels of blood lipid in rats. Hematoxylin-eosin staining (H-E staining) was used to observe the injury of liver tissue and aorta tissue. Apoptosis of liver tissue was detected by TUNEL staining. The levels of interleukin-1β (IL-1β), IL-6 and inducible nitric oxide synthase (iNOS) in peripheral blood were detected by enzyme linked immunosorbent assay (ELISA). The expression of PCSK9, Toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB) P65 and tumor necrosis factor α (TNF-α) were detected by Western blotting.

·Compared with the control group, obesity index and insulin level in the model group were significantly increased (all P=0.000); the apoptosis rate of liver cells was significantly increased (P=0.000); the level of high density lipoprotein cholesterol (HDL-C) was significantly decreased, while the levels of low density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and triacylglycerol (TAG) were significantly increased (all P=0.000); the levels of IL-1β, IL-6 and iNOS were significantly increased (all P=0.000); TLR4, NF-κB P65 protein activation and TNF-α expression were significantly increased (all P=0.000); the liver tissue and aorta tissue were significantly damaged. After interferenceof Pcsk9 gene expression, compared with the model group, obesity index and insulin level in the high fat＋Pcsk9-shRNA group were significantly reduced (P=0.007, P=0.000); the apoptosis rate of liver cells was significantly reduced (P=0.000); the level of HDL-C was significantly increased while the levels of LDL-C, TC and TAG were significantly decreased (all P=0.000); the levels of IL-1β, IL-6 and iNOS were significantly decreased (all P=0.000); TLR4, NF-κB P65 protein activation and TNF-α expression were significantly decreased (all P=0.000); the histopathological lesions of liver tissue and aorta tissue were improved.

·Knockdown of Pcsk9 gene can reduce obesity index, insulin level, blood lipid index and inflammatory response in the rats with NAFLD and atherosclerosis, and inhibit the activation of TLR4 and NF-κB P65 protein, thereby improving the injury of liver and aortic tissue in rats.