1.Losartan attenuates vascular remodeling of the aorta in spontaneously hypertensive rats and the underlying mechanism
Fangxiong LI ; Ruizheng SHI ; Meichun LIAO ; Jianzhe LI ; Shixun LI ; Wei PAN ; Tianlun YANG ; Guogang ZHANG
Journal of Central South University(Medical Sciences) 2010;35(8):807-813
Objective To determine the effect of losartan on vascular remodeling and the underlying mechanism in spontaneously hypertensive rats(SHR). Methods SHR of 12 weeks old were given losartan orally [0,15,30 mg/(kg·d),n=12]. The tail arterial pressure was measured every week.Eight weeks later, the pathological changes and p22phox expression in the thoracic aorta, the activity of catalase (CAT), the contents of H2O2 and AngⅡ in the plasma were evaluated. Results Blood pressure was increased in the SHR accompanied by the thickened wall and increased p22phox expression in the thoracic aorta. The plasma levels of H2O2 and AngⅡwere elevated while the CAT level was decreased in the SHR. Administration of losartan reversed the thickened wall and increased the CAT activity concomitantly with the decreased plasma levels of H2O2 and p22phox expression in the SHR. The plasma level of AngⅡincreased after the losartan treatment. Conclusion Oxidative stress induces the vascular remodeling of the aorta in the SHR. Losartan can reverse the vascular remodeling through down-regulating p22phox expression and inhibiting the oxidative stress.
2.Effect of Panax notoginseng on genes expression of CYP and GST in lung tissues of rats.
Xiufen YANG ; Meichun LIAO ; Ziming YANG ; Jingjing GUO ; Qianqian GAO
China Journal of Chinese Materia Medica 2009;34(17):2236-2240
OBJECTIVETo examine the effects of Panax notoginseng on the expression of cytochrome P450 (CYP) genes and glutathione S-transferase (GST) genes in lung tissues of male SD rats.
METHODRats were administered P. notoginseng 2 or 4 g X kg(-1) bw/d by gavage daily for 15 days. The levels of gene expression of CYP1A1, CYP1A2, CYP1B1, CYP2B1, CYP2E1, CYP3A1, CYP4A1 and glutathione S-transferase ml (GST-ml) and glutathione S-transferase pi (GST-pi) were examined by quantitative real-time reverse-transcription polymerase chain reaction (quantitative real time-RT-PCR) assays.
RESULTThe expression of CYP2E1, CYP1A2 and GST-pi genes was not changed by P. notoginseng treatment, however, 2 g * kg-1 dose of P. notoginseng gave a 4.00-fold (P < 0.05) induction of CYP3A1 mRNA. P. notoginseng significantly increased mRNA expressions of GSTml (1.64-fold, P <0. 05 and 1.53-fold, P > 0.05) and CYP1A1 (3.44-fold, P > 0.05 and 6.05-fold, P < 0.05) in the 2 g x kg(-1) and 4 g x kg(-1) bw/d treatment groups, respectively, but P. notoginseng had a inhibitory tendency on mRNA expressions of CYP1B1 (0.81-fold, P > 0.05 and 0.38-fold, P > 0.05) and significantly inhibited the expressions of CYP2B1 (0.47-fold, P < 0.05 and 0.50-fold, P < 0.05) and CYP4A1 (0.54-fold, P < 0.05 and 0. 72-fold, P < 0.05) genes in the two groups.
CONCLUSIONA specific effect of P. notoginseng on the expression of different cytochrome P-450 genes or glutathione S-transferase genes in the lung tissues of rats was observed in this investigation. These findings would be very important and helpful for studying the mechanism of action of P. notoginseng and its reasonable use in clinic.
Animals ; Cytochrome P-450 Enzyme System ; genetics ; metabolism ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Gene Expression ; drug effects ; Glutathione Transferase ; genetics ; metabolism ; Lung ; drug effects ; enzymology ; Male ; Panax notoginseng ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley
3.Effect of Panax notoginseng on genes expression of CYP and GST in liver tissues of rats.
Xiufen YANG ; Meichun LIAO ; Ziming YANG ; Jingjing GUO ; Qianqian GAO
China Journal of Chinese Materia Medica 2009;34(18):2390-2393
OBJECTIVETo examine the effects of Panax notoginseng on the expression of cytochrome P450 (CYP) genes and glutathione S-trans-ferase (GST) genes in liver tissues of male SD rats.
METHODRats were administered P. notoginseng 2 or 4 g x kg(-1) bw/d by gavage daily for 14 days. The levels of gene expression of CYP1A1, CYP1A2, CYP2B1, CYP2E1, CYP3A1, CYP4A1, and GSTml, GST-pi were examined by quantitative real-time reverse-transcription polymerase chain reaction (quantitative real time-RT-PCR) assays.
RESULTThe expression of CYP1A1, CYP1A2, CYP2E1, CYP3A1, GSTml and GST-pi genes was not changed by 2 or 4 g x kg(-1) P. notoginseng treatment, But P. notoginseng significantly inhibited mRNA expressions of CYP2B1 (0.48-fold, P < 0.05, and 0.61-fold, P < 0.05, respectively) and CYP 4A1 (0.69-fold, and 0. 51-fold, respectively).
CONCLUSIONP. notoginseng had a special inhibitory selectivity on the expression of CYP2B1 and CYP4A1 genes in liver tissues of rats, which indicated it may be one of the mechanisms of actions of P. notoginseng. P. notoginseng had no effects on the expressions of CYP1A1, CYP1A2, CYP2E1 and CYP3A1 genes, which suggested when P. notoginseng co-administrated with those drugs metabolized by the above major metabolizing enzymes in liver, metabolic herb-drug interactions would not be happened.
Animals ; Cytochrome P-450 Enzyme System ; genetics ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression ; drug effects ; Glutathione Transferase ; genetics ; metabolism ; Liver ; drug effects ; enzymology ; Male ; Panax notoginseng ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley