Rui Fu
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1、A novel role for thyroid-stimulating hormone: Up-regulation of hepatic 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase expression through the cyclic adenosine monophosphate/protein kinase A/cyclic adenosine monophosphate-responsive element binding protei

摘要:Elevated thyroid-stimulating hormone (TSH) and hypercholesterolemia commonly coexist, as typically seen in hypothyroidism, but there is no known mechanism directly linking the two. Here, we demonstrated that in liver cells, TSH promoted the expression of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR), a rate-limiting enzyme in cholesterol synthesis, by acting on the TSH receptor in hepatocyte membranes and stimulating the cyclic adenosine monophosphate / protein kinase A / cyclic adenosine monophosphate-responsive element binding protein (cAMP/PKA/CREB) signaling system. In thyroidectomized rats, the production of endogenous thyroid hormone was eliminated and endogenous TSH was suppressed through pituitary suppression with constant administration of exogenous thyroid hormone, and hepatic HMGCR expression was increased by administration of exogenous TSH. These results suggested that TSH could up-regulate hepatic HMGCR expression, which indicated a potential mechanism for hypercholesterolemia involving direct action of TSH on the liver. (HEPATOLOGY 2010)
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2、Insight into the pharmacokinetic behavior of tanshinone IIA in the treatment of Crohn’s disease: comparative data for tanshinone IIA and its two glucuronidated metabolites in normal and recurrent colitis models after oral administration

摘要:1. Previous reports implied that tanshinone IIA (TSA) may offer potential benefits for Crohn’s disease (CD). However, the detailed pharmacokinetic behavior of TSA in the treatment of colitis remain unclear. Herein, a recurrent trinitrobenzene sulfonic acid (TNBS)-colitis mouse model was used to investigate whether TSA possesses favorable pharmacokinetic and colonic distribution profiles to serve as a candidate drug.2. Although the systemic TSA exposures were low (AUC0-t approximately 330 ng*h/ml) in both the normal and colitis models after oral administration TSA 20 mg/kg, high levels of TSA were found in the gastrointestinal tract (GI). Such a GI exposure of TSA in colitis mice is adequate to exert anti-inflammatory effects as observed in various in vitro studies.3. Interestingly, colonic TSA exposure in the colitis mouse model was much lower than that in the normal mice, which may be explained by a significant upregulation of colonic UDP-glucuronosyltransferase (Ugt)1a9 expression and a higher plasma concentration of TSA glucuronides in the model mice at 0.5, 1 and 2 h after TSA administration.4. Together, these results reveal high accumulation at the site of inflammation and minimal systemic concentration of TSA, which are favorable pharmacokinetic behaviors to meet the requirements for CD treatment.
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