Background Myocardial infarction （MI） has likely contributed to the increased prevalence of heart failure （HF）. As a result of re- duced cardiac function, splanchnic blood flow decreases, causing ischemia in villi...Background Myocardial infarction （MI） has likely contributed to the increased prevalence of heart failure （HF）. As a result of re- duced cardiac function, splanchnic blood flow decreases, causing ischemia in villi and damage to the intestinal barrier. The induction of heme oxygenase-1 （HO-1） could prevent, or lessen the effects of stress and inflammation. Thus, the effect and mechanism thereof of HO-1 on the intestines of rats with HF was investigated. Methods Male Wistar rats with heart failure through ligation of the left coronary artery were identified with an left ventricular ejection fraction of 〈 45% through echocardiography and then divided into various experimental groups based on the type of peritoneal injection they received [MI： saline; MI ＋ Cobalt protoporphyrin （CoPP）： CoPP solution; and MI ＋ Tin mesoporphyrin IX dichloride （SnMP）： SnMP solution]. The control group was comprised of rats without coronary ligation. Echocardiogra- phy was performed before ligation for a baseline and eight weeks after ligation in order to evaluate the cardiac function of the rats. The bac- terial translocation （BT） incidence, mesenteric microcirculation, amount of endotoxins in the vein serum, ileum levels of HO- 1, carbon oxide （CO）, nitric oxide （NO）, intedeuldn （IL）-10, turnour necrosis factor-et （TNF-ct）, and the ileum morphology were determined eight weeks after the operation. Results The rats receiving MI ＋ CoPP injections exhibited a recovery in cardiac function, an amelioration of mesenteric microcirculation and change in morphology, a lower BT incidence, a reduction in serum and ileac NO and TNF-ct levels, and an elevation in ileac HO-1, CO, and interleukin-10 （[L-10） levels compared to the MI group （P 〈 0.05）. The rats that received the MI ＋ SnMP injections exhibited results inverse to the MI （P 〈 0.05） group. Conclusions HO-1 exerted a protective effect on the intestines of rats with HF by inhibiting the inflammation and amelioration of microcirculation through the CO pathway. This protective effect could be independent from the recovery of cardiac function.展开更多
AIM： To investigate the effects of heme oxygenase-1 （HO-1） against oxidant-induced injury caused by bile duct ligation （BDL）.METHODS： Either cobalt protoporphyrin （CoPP）, a HO-1 inducer, or saline were injecte...AIM： To investigate the effects of heme oxygenase-1 （HO-1） against oxidant-induced injury caused by bile duct ligation （BDL）.METHODS： Either cobalt protoporphyrin （CoPP）, a HO-1 inducer, or saline were injected intraperitoneally in male SD-rats. Three days later, BDL or sham-operations were performed. Rats were sacrificed 3 wk after BDL and livers were harvested for histology. Fibrosis was evaluated by sirius red staining and image analysis. Alpha-smooth muscular actin, which indicates activation of stellate cells, was detected by immunohistochemical staining, and q/tokine and collagen- Iα （Col- I α） mRNA expression was detected using RNase protection assays.RESULTS： Serum alanine transaminase increased 8-fold above normal levels one day after BDL. Surprisingly, enzyme release was not reduced in rats receiving CoPP. Liver fibrosis was evaluated 3 wk after BDL and the sirius red-positive area was found to be increased to about 7.8%. However, in CoPP pretreated rats sirius redpositive areas were increased to about 11.7% after BDL. Collagen-1 α and TGF-β mRNA increased significantly by BDL. Again, this effect was increased by HO-1 overexpression.CONCLUSION： Hepatic fibrosis due to BDL is not reduced by the HO-1 inducer CoPP. In contrast, HO-1 overexpression increases liver injury in rats under conditions of experimental chronic cholestasis.展开更多
AIM： To study the effect of bilirubin on the oxidative liver status and the activity and expression of heine oxygenase-1 （HO-1） in rat liver injury induced by prehepatic portal hypertension. METHODS： Wistar male r...AIM： To study the effect of bilirubin on the oxidative liver status and the activity and expression of heine oxygenase-1 （HO-1） in rat liver injury induced by prehepatic portal hypertension. METHODS： Wistar male rats, weighing 200-250 g, were divided at random into two groups： one group with prehepatic portal hypertension （PH） induced by regulated prehepatic portal vein ligation （PPVL） and the other group corresponded to sham operated rats. Portal pressure, oxidative stress parameters, antioxidant enzymes, HO-1 activity and expression and hepatic sinusoidal vasodilatation were measured. RESULTS： In PPVL rats oxidative stress was evidenced by a marked increase in thiobarbituric acid reactive substances （TBARS） content and a decrease in reduced glutathione （GSH） levels. The activities of liver antioxidant enzymes, superoxide dismutase （SOD）, catalase （CAT） and glutathione peroxidase （GSH-Px） were also diminished while activity and expression of HO-1 were enhanced. Administration of bilirubin （5μmol/kg body weight） 24 h before the end of the experiment entirely prevented all these effects. Pretreatment with Sn-protoporphyrin IX （Sn-PPIX） （100 μg/kg body weight, i.p.）, a potent inhibitor of HO, completely abolished the oxidative stress and provoked a slight decrease in liver GSH levels as well as an increase in lipid peroxidation. Besides, carbon monoxide, another heme catabolic product, induced a significant increase in sinusoidal hepatic areas in PPVL group. Pretreatment of PPVL rats with Sn-PPIX totally prevented this effect CONCLUSION： These results suggest a beneficial role of HO-1 overexpression in prehepatic portal hypertensive rats.展开更多
It aims to analyze the impact heme oxygenase -1 （heme oxygenase 1, HO-1） on regulating factors of human hepatoma cell HepG2＇s cell cycle, through constructing recombinant vector of pcDNA3.1 containing wild-type and...It aims to analyze the impact heme oxygenase -1 （heme oxygenase 1, HO-1） on regulating factors of human hepatoma cell HepG2＇s cell cycle, through constructing recombinant vector of pcDNA3.1 containing wild-type and mutant HO-1 gene （＋）-wtHO-1 and pcDNA3.1 （＋）-mHO-1G143H. By using the method of liposome-mediated, the recombinant vector was transfected hepatoma cell line HepG2. And the transfected one with empty vector was treated as a control group. By the selection of G418, stable expression of wild-type and mutant HO-1 in HepG2 liver cancer cell lines were established. Use the blot of semi-quantitative RT-PCR and Western to test transfected cell lines expressing levels of riO-1 mRNA and protein. As HO-1 expression in stably transfected cell lines altered, we use Western blot to test transfected cell lines P21, P27 protein expression levels. As result shows, we got 1 HO-over-expression of wild-type and mutant in HepG2 cells; wild- type and mutant＇s over expression of HO-1 can induce the expression of tumor suppressor genes p21 and p27.we got the conclusion that HO-l＇s over-expression of tumor suppressor genes p21 and p27 is unrelated to the expression of heme decomposition products. HO-1 may regulate the expression of p21 and p27 through other mechanisms.展开更多
文摘Background Myocardial infarction （MI） has likely contributed to the increased prevalence of heart failure （HF）. As a result of re- duced cardiac function, splanchnic blood flow decreases, causing ischemia in villi and damage to the intestinal barrier. The induction of heme oxygenase-1 （HO-1） could prevent, or lessen the effects of stress and inflammation. Thus, the effect and mechanism thereof of HO-1 on the intestines of rats with HF was investigated. Methods Male Wistar rats with heart failure through ligation of the left coronary artery were identified with an left ventricular ejection fraction of 〈 45% through echocardiography and then divided into various experimental groups based on the type of peritoneal injection they received [MI： saline; MI ＋ Cobalt protoporphyrin （CoPP）： CoPP solution; and MI ＋ Tin mesoporphyrin IX dichloride （SnMP）： SnMP solution]. The control group was comprised of rats without coronary ligation. Echocardiogra- phy was performed before ligation for a baseline and eight weeks after ligation in order to evaluate the cardiac function of the rats. The bac- terial translocation （BT） incidence, mesenteric microcirculation, amount of endotoxins in the vein serum, ileum levels of HO- 1, carbon oxide （CO）, nitric oxide （NO）, intedeuldn （IL）-10, turnour necrosis factor-et （TNF-ct）, and the ileum morphology were determined eight weeks after the operation. Results The rats receiving MI ＋ CoPP injections exhibited a recovery in cardiac function, an amelioration of mesenteric microcirculation and change in morphology, a lower BT incidence, a reduction in serum and ileac NO and TNF-ct levels, and an elevation in ileac HO-1, CO, and interleukin-10 （[L-10） levels compared to the MI group （P 〈 0.05）. The rats that received the MI ＋ SnMP injections exhibited results inverse to the MI （P 〈 0.05） group. Conclusions HO-1 exerted a protective effect on the intestines of rats with HF by inhibiting the inflammation and amelioration of microcirculation through the CO pathway. This protective effect could be independent from the recovery of cardiac function.
基金grants from the National Institute of Health and by a grant from the Deutsche Forschungsgemeinschaft, No. FR 1644/4-1
文摘AIM： To investigate the effects of heme oxygenase-1 （HO-1） against oxidant-induced injury caused by bile duct ligation （BDL）.METHODS： Either cobalt protoporphyrin （CoPP）, a HO-1 inducer, or saline were injected intraperitoneally in male SD-rats. Three days later, BDL or sham-operations were performed. Rats were sacrificed 3 wk after BDL and livers were harvested for histology. Fibrosis was evaluated by sirius red staining and image analysis. Alpha-smooth muscular actin, which indicates activation of stellate cells, was detected by immunohistochemical staining, and q/tokine and collagen- Iα （Col- I α） mRNA expression was detected using RNase protection assays.RESULTS： Serum alanine transaminase increased 8-fold above normal levels one day after BDL. Surprisingly, enzyme release was not reduced in rats receiving CoPP. Liver fibrosis was evaluated 3 wk after BDL and the sirius red-positive area was found to be increased to about 7.8%. However, in CoPP pretreated rats sirius redpositive areas were increased to about 11.7% after BDL. Collagen-1 α and TGF-β mRNA increased significantly by BDL. Again, this effect was increased by HO-1 overexpression.CONCLUSION： Hepatic fibrosis due to BDL is not reduced by the HO-1 inducer CoPP. In contrast, HO-1 overexpression increases liver injury in rats under conditions of experimental chronic cholestasis.
基金Supported by Grants from the University of Buenos Aires, Buenos Aires, Argentina and CONICET, Buenos Aires, Argentina
文摘AIM： To study the effect of bilirubin on the oxidative liver status and the activity and expression of heine oxygenase-1 （HO-1） in rat liver injury induced by prehepatic portal hypertension. METHODS： Wistar male rats, weighing 200-250 g, were divided at random into two groups： one group with prehepatic portal hypertension （PH） induced by regulated prehepatic portal vein ligation （PPVL） and the other group corresponded to sham operated rats. Portal pressure, oxidative stress parameters, antioxidant enzymes, HO-1 activity and expression and hepatic sinusoidal vasodilatation were measured. RESULTS： In PPVL rats oxidative stress was evidenced by a marked increase in thiobarbituric acid reactive substances （TBARS） content and a decrease in reduced glutathione （GSH） levels. The activities of liver antioxidant enzymes, superoxide dismutase （SOD）, catalase （CAT） and glutathione peroxidase （GSH-Px） were also diminished while activity and expression of HO-1 were enhanced. Administration of bilirubin （5μmol/kg body weight） 24 h before the end of the experiment entirely prevented all these effects. Pretreatment with Sn-protoporphyrin IX （Sn-PPIX） （100 μg/kg body weight, i.p.）, a potent inhibitor of HO, completely abolished the oxidative stress and provoked a slight decrease in liver GSH levels as well as an increase in lipid peroxidation. Besides, carbon monoxide, another heme catabolic product, induced a significant increase in sinusoidal hepatic areas in PPVL group. Pretreatment of PPVL rats with Sn-PPIX totally prevented this effect CONCLUSION： These results suggest a beneficial role of HO-1 overexpression in prehepatic portal hypertensive rats.
文摘It aims to analyze the impact heme oxygenase -1 （heme oxygenase 1, HO-1） on regulating factors of human hepatoma cell HepG2＇s cell cycle, through constructing recombinant vector of pcDNA3.1 containing wild-type and mutant HO-1 gene （＋）-wtHO-1 and pcDNA3.1 （＋）-mHO-1G143H. By using the method of liposome-mediated, the recombinant vector was transfected hepatoma cell line HepG2. And the transfected one with empty vector was treated as a control group. By the selection of G418, stable expression of wild-type and mutant HO-1 in HepG2 liver cancer cell lines were established. Use the blot of semi-quantitative RT-PCR and Western to test transfected cell lines expressing levels of riO-1 mRNA and protein. As HO-1 expression in stably transfected cell lines altered, we use Western blot to test transfected cell lines P21, P27 protein expression levels. As result shows, we got 1 HO-over-expression of wild-type and mutant in HepG2 cells; wild- type and mutant＇s over expression of HO-1 can induce the expression of tumor suppressor genes p21 and p27.we got the conclusion that HO-l＇s over-expression of tumor suppressor genes p21 and p27 is unrelated to the expression of heme decomposition products. HO-1 may regulate the expression of p21 and p27 through other mechanisms.
