Effect of Shuangyu Tiaozhi Decoction on NPC1L1 and ABCG8 in Intestine of Hyperlipemic Model Rats / 中国实验方剂学杂志

Objective:To observe the expression levels of niemann-pick C1-like 1 (NPC1L1) and adenosine triphosphate-binding cassette transporters G8 (ABCG8) in intestine of hyperlipidemic model rats, in order to investigate the therapeutic mechanism of Shuangyu Tiaozhi decoction on hyperlipidemia. Method:A total of 40 SD rats were selected, including 8 for normal control group. The remaining 32 rats were used to establish hyperlipemic model. After modeling, the rats were randomly divided into the model group (equivalent normal saline), the high and low-dose Shuangyu Tiaozhi groups (15.6, 7.8 g·kg-1), and the Simvastatin group (4 mg·kg-1), with 8 in each group. They were given drugs by gavage for 8 weeks. The levels of total cholesterol (TC), triglyceride (TG) in serum and total cholesterol (TTC), free cholesterol (FTC) in liver of rats in each group were determined by biochemical and enzymatic methods. The morphological changes of liver were observed by hematoxylin-eosin (HE) staining, and the levels of expressions of NPC1L1, ABCG8 and liver X receptor-α (LXR-α) in intestine were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot. The expression of ABCG8 protein was determined by immunohistochemistry. Result:After successful replication of the hyperlipidemia model, the blood lipid level was abnormally increased, and the liver steatosis became obvious in the model group compared with the normal control group. The expression levels of NPC1L1, LXR-α and ABCG8 increased significantly (PPα were significantly down-regulated, but ABCG8 was obviously up-regulated in a dose-dependent manner (PPPPPPConclusion:Shuangyu Tiaozhi decoction can reduce the blood lipid level of hyperlipemic rat model by reducing the absorption of cholesterol. Its mechanism may be correlated with the down-regulation of NPC1L1 expression and the up-regulation of ABCG8 expression.

Distribution characteristics of NPC1L1 gene 1 735 C>G polymorphism and relationship between serum lipid levels and obesity in Guangxi Han population / 重庆医学

Objective To analyze the distributional characteristics of NPC1L1 1 735 C>G polymorphism and the relation-ship between serum lipid levels and obesity in Guangxi Han population.Methods Genotyping of the NPC1L1 1 735 C>G poly-morphism of 409 cases of Han was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis in all subjects.The relationship of different genotypes in blood lipid levels and obesity were evaluated.Re-sults The frequency of CC,CG and GG genotypes was 39.40%,46.00% and 14.60% in Han.The frequency of C and G alleles was 62.35% and 37.65% in Han.The levels of BMI,LDL-C,ApoB was different among the three genotypes (P G polymorphism in NPC1L1 gene may be correla-ted with serum lipid profiles and obesity,the G allele might increase the risk of hyperlipemia and obesity.

Intestinal and Hepatic Niemann-Pick C1-Like 1

Polytopic transmembrane protein, Niemann-Pick C1-Like 1 (NPC1L1) is localized at the apical membrane of enterocytes and the canalicular membrane of hepatocytes. It mediates intestinal cholesterol absorption and prevents extensive loss of cholesterol by transporting biliary cholesterol into hepatocytes. NPC1L1 is a molecular target of ezetimibe, an agent for hypercholesterolemia. Recently, NPC1L1 inhibition has been shown to prevent metabolic disorders such as fatty liver disease, obesity, diabetes, and atherosclerosis. In this review, the identification and characterization of NPC1L1, NPC1L1-dependent cholesterol transport, the relationship with pathogenesis of metabolic disease and its newly introduced function for virus entry are discussed.

The advanced development of Niemann-Pick C1 Like 1 / 肠外与肠内营养

Identification and characterization of Niemann-Pick C1 Like 1 (NPC1L1) has established NPC1L1 as an essential protein in the intestinal cholesterol absorption process,and NPC1L1 is the molecular target of ezetimibe, which is a cholesterol absorption inhibitor. The expression of the gene and protein of NPC1L1 may be regulated by some nuclear receptors. Lack of NPC1L1 auses a nearly complete protection from the development of atherosclerosis in apoE-/- mice c, which provides new target for the treatment for atherosclerosis and cardiovascular disease.