RESUMEN
Objective:To observe the effect of Shuangyu Tiaozhi decoction on B-type scavenger receptor （SRB1）/cholesterol 7<italic>α</italic>-hydroxylase protein （CYP7A1）/farnesol X receptor （FXR） signaling pathway in liver of hypercholesterolemic rats， and its mechanism in reducing blood lipid. Method:Among 40 SD rats， 8 were randomly selected as normal group， and the remaining 32 were successfully established as hypercholesterolemic model， and randomly divided into 4 groups： model group， low and high-dose Shuangyu Tiaozhi decoction groups （7.8， 15.6 g·kg<sup>-1</sup>）， and simvastatin group （4 mg·kg<sup>-1</sup>）， with 8 rats in each group. The drugs were continuously given for 8 weeks. Serum total cholesterol （TC）， triglyceride （TG） and liver TC，free cholesterol （FC） and total bile acid （TBA） were measured. The pathomorphological changes in liver were observed by Hematoxylin and eosin （HE） Staining. The mRNA and protein expressions of SRB1， CYP7A1 and FXR were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. The immunohistochemistry was used to detect CYP7A1 and FXR expressions in liver. Result:Compared with the normal group， TC， TG， FC levels in the model group were significantly increased， while the TBA level was markedly decreased， the morphology showed obvious liver steatosis， and significant declines in expressions of SRB1， CYP7A1， FXR were observed by Real-time PCR， Western blot and immunohistochemistry assays （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the model group， the levels of TC，TG，FC in each treatment group were reduced significantly， and the TBA level was increased markedly， the liver steatosis decreased significantly， the results of Real-time PCR， Western blot and immunohistochemistry assays showed significant increase in the expressions of SRB1， CYP7A1， FXR （<italic>P</italic><0.05， <italic>P</italic><0.01）. The therapeutic effect of high-dose Shuangyu Tiaozhi decoction group was more remarkable than that in low-dose Shuangyu Tiaozhi Decoction group （<italic>P</italic><0.05）， with no obvious difference compared with simvastatin group. Conclusion:Shuangyu Tiaozhi decoction can promote hepatic RCT and synthesize bile acid by up-regulating SRB1/CYP7A1/FXR signaling pathway， so as to reduce the blood lipid levels and improve hepatic lipid metabolism of hypercholesterolemic rats.
RESUMEN
The efflux of cholesterol from macrophage to liver is known as reverse cholesterol transport (RCT). Impairedcholesterol efflux leads to cholesterol accumulation in macrophages. Therefore, how to increasing cholesterol effluxmay be an effective strategy for atherosclerosis prevention. Key molecules that play a vital role in the efflux ofcholesterol from macrophage are Adenosin Tri Phosphate (ATP)-binding casette transporters A1 and G. This study wasundertaken to clarify the effect of Catechins on the expression of specific transporters such as ATP-binding cassettesub-family A member 1 (ABCA1), ATP-binding cassette sub-family G member 1 (ABCG1) from macrophage to liver,and scavenger receptor class B type I (SRB1). This research was done on Wistar rats induced atherogenic diets. SRB1is one of the transporters to facilitate the delivery of cholesterol from the macrophage to the liver. The SRB1 pathwaymediated the selective uptake of cholesteryl ester. Catechins significantly increased the mRNA expression of ABCA1and ABCG1 in aorta as well as SRB1 of liver also increased. Thus, Catechins decreased the total cholesterol levels inaorta and serum. Catechins can be developed as a potential agent to increase ABCA1 to inhibit atherogenesis process.In conclusion, this study indicates that the potential anti-atherogenic properties of Catechins could be explained, atleast in part, as being due to upregulated expression of ABCA1, ABCG1, and SRB1 through activation liver X receptorsignaling pathway
RESUMEN
The efflux of cholesterol from macrophage to liver is known as reverse cholesterol transport (RCT). Impairedcholesterol efflux leads to cholesterol accumulation in macrophages. Therefore, how to increasing cholesterol effluxmay be an effective strategy for atherosclerosis prevention. Key molecules that play a vital role in the efflux ofcholesterol from macrophage are Adenosin Tri Phosphate (ATP)-binding casette transporters A1 and G. This study wasundertaken to clarify the effect of Catechins on the expression of specific transporters such as ATP-binding cassettesub-family A member 1 (ABCA1), ATP-binding cassette sub-family G member 1 (ABCG1) from macrophage to liver,and scavenger receptor class B type I (SRB1). This research was done on Wistar rats induced atherogenic diets. SRB1is one of the transporters to facilitate the delivery of cholesterol from the macrophage to the liver. The SRB1 pathwaymediated the selective uptake of cholesteryl ester. Catechins significantly increased the mRNA expression of ABCA1and ABCG1 in aorta as well as SRB1 of liver also increased. Thus, Catechins decreased the total cholesterol levels inaorta and serum. Catechins can be developed as a potential agent to increase ABCA1 to inhibit atherogenesis process.In conclusion, this study indicates that the potential anti-atherogenic properties of Catechins could be explained, atleast in part, as being due to upregulated expression of ABCA1, ABCG1, and SRB1 through activation liver X receptorsignaling pathway.
RESUMEN
Objective To study the effect of tumor size on the expression of adrenal cholesterol homeostasis mole -cules in H22 hepatoma-bearing mice.Methods Two hundred and twenty mice were injected with H 22 hepatoma cells to their right armpit.On the 11th day after injection, the mice were sorted according to the tumor size .18 mice with large tumor (large tumor group) and 18 mice with small tumor (small tumor group) were sacrificed, and the tumors were weighed.A control group consisting of 18 normal Kunming mice was also included in this study .The plasma TC, TG and HDL-C were detected using total cholesterol , triglycerides or HDL-C assay kits , respectively .The mRNA expressions of Srb1, Ldlr, Npc1, Npc2, Stard3, Hmgcr, Lipe, Acat1, Abca1, Abcg1, Srebp-1c, Lxrα, Lxrβ, Rxrα, Apoa1 and Apoe were tested by real-time quantitative RT-PCR ( qRT-PCR ) , and Gapdh and β-actin were used for normalization .SRB1 and ApoA1 proteins were analyzed by Western blot .Results The tumor weight was significantly higher in the large tumor group than that in the small tumor group (P<0.05).Compared with the control group , the plasma HDL-C was significant-ly decreased in the two hepatoma groups (P<0.05).The expression levels of Srb1, Ldlr, Apoa1 mRNA and SRB1 protein were significantly increased in the large tumor group (P<0.05 for all).The ApoA1 protein level was significantly higher in the large tumor group than that in the small tumor group (P<0.05).The expressions of Acat1, Lipe, Abca1 and Abcg1 mRNA were significantly lower in the large tumor group than those in the small tumor group (P<0.05 for all).However, the expressions of Srebp-1c, Lxrαand RxrαmRNA were not significantly changed , then, Srebp-1c, Lxrβand RxrαmRNA expressions were significantly up-regulated in the small tumor group (P<0.05).The expressions of Hmgcr and Apoe mR-NA were not significantly different in the two groups .Conclusions In hepatoma-bearing mice , due to the adaptation to tumor-induced chronic stress response , the adrenal cortical cells can effectively utilize intracellular cholesterol to synthetize cortical hormones .