Objective To investigate the possible involvement of erythropoietin （EPO）/erythropoietin receptor （EPOR） system in neovascularization and vascular regeneration in diabetic retinopathy （DR）. Methods EPOR positive...Objective To investigate the possible involvement of erythropoietin （EPO）/erythropoietin receptor （EPOR） system in neovascularization and vascular regeneration in diabetic retinopathy （DR）. Methods EPOR positive circulating progenitor cells （CPCs： CD34^＋） and endothelial progenitor cells （EPCs： CD34^＋KDR^＋） were assessed by flow cytometry in type 2 diabetic patients with different stages of DR. The cohort consisted of age- and sex-matched control patients without diabetes （n=7）, non-prolif- erative DR （NPDR, n=7）, proliferative DR （PDR, n=8）, and PDR complicated with diabetic nephropathy （PDR-DN, n=7）. Results The numbers of EPOR^＋ CPCs and EPOR^＋ EPCs were reduced remarkably in NPDR corn pared with the control group （both P（0.01）, whereas rebounded in PDR and PDR-DN groups in varying degrees. Similar changes were observed in respect of the proportion of EPOR^＋ CPCs in CPCs （NPDR vs. control, P（0.01） and that of EPOR^＋ EPCs in EPCs （NPDR vs. control, P〈0.05）. Conclusion Exogenous EPO, mediated via the EPO/EPOR system of EPCs, may alleviate the impaired vascular regeneration in NPDR, whereas it might aggravate retinal neovascularization in PDR due to a rebound of EPOR^＋ EPCs associated with ischemia.展开更多
AIM To examine the changes of the ghrelin/ghrelin O-acyltransferase(GOAT) axis and the mammalian target of rapamycin(m TOR) pathway in the hypothalamus after sleeve gastrectomy.METHODS A total of 30 obese type-2 diabe...AIM To examine the changes of the ghrelin/ghrelin O-acyltransferase(GOAT) axis and the mammalian target of rapamycin(m TOR) pathway in the hypothalamus after sleeve gastrectomy.METHODS A total of 30 obese type-2 diabetes Sprague-Dawley(SD) rats, 6 wk of age, fed with high-sugar and highfat fodder for 2 mo plus intraperitoneal injection of streptozotocin were randomly divided into three groups: non-operation group(S0 group, n = 10), sham operation group(Sh group, n = 10) and sleeve gastrectomy group(SG group, n = 10). Data of body mass, food intake, oral glucose tolerance test(OGTT), acylated ghrelin(AG) and total ghrelin(TG) were collected and measured at the first day(when the rats were 6 wk old), preoperative day 3 and postoperative week 8. The m RNA expression of preproghrelin, GOAT and neuropeptide Y(NPY), and protein expression of ghrelin, GOAT, GHSR and the m TOR pathway(p-Akt, p-m TOR and p-S6) were measured in the hypothalamus.RESULTS SG can significantly improve metabolic symptoms by reducing body mass and food intake. The obese rats showed lower serum TG levels and no change in AG, but the ratio of AG/TG was increased. When compared with the S0 and Sh groups, the SG group showed decreased TG(1482.03 ± 26.55, 1481.49 ± 23.30 and 1206.63 ± 52.02 ng/L, respectively, P < 0.05), but unchanged AG(153.06 ± 13.74, 155.37 ± 19.30 and 144.44 ± 16.689 ng/L, respectively, P > 0.05). As a result, the ratio of AG/TG further increased in the SG group(0.103 ± 0.009, 0.105 ± 0.013 and 0.12 ± 0.016, respectively, P < 0.05). When compared with the S0 group, SG suppressed m RNA and protein levels of preproghrelin(0.63 ± 0.12 vs 0.5 ± 0.11, P < 0.05) and GOAT(0.96 ± 0.09 vs 0.87 ± 0.08, P < 0.05), but did not change NPY m RNA expression(0.61 ± 0.04 vs 0.65 ± 0.07, P > 0.05) in the hypothalamus. The protein levels of p-Akt, p-m TOR and p-S6 were higher in the SG group, which indicated that the hypothalamic m TOR pathway was activated after SG at the postoperative week 8. CONCLUSION The reduction of ghrelin expression and activation of the m TOR pathway might have opposite effects on food intake, as SG improves obesity and T2 DM.展开更多
基金Supported by Sciences and Technology Commission of Shanghai Municipality (08ZR1422100 and 08410701200)
文摘Objective To investigate the possible involvement of erythropoietin （EPO）/erythropoietin receptor （EPOR） system in neovascularization and vascular regeneration in diabetic retinopathy （DR）. Methods EPOR positive circulating progenitor cells （CPCs： CD34^＋） and endothelial progenitor cells （EPCs： CD34^＋KDR^＋） were assessed by flow cytometry in type 2 diabetic patients with different stages of DR. The cohort consisted of age- and sex-matched control patients without diabetes （n=7）, non-prolif- erative DR （NPDR, n=7）, proliferative DR （PDR, n=8）, and PDR complicated with diabetic nephropathy （PDR-DN, n=7）. Results The numbers of EPOR^＋ CPCs and EPOR^＋ EPCs were reduced remarkably in NPDR corn pared with the control group （both P（0.01）, whereas rebounded in PDR and PDR-DN groups in varying degrees. Similar changes were observed in respect of the proportion of EPOR^＋ CPCs in CPCs （NPDR vs. control, P（0.01） and that of EPOR^＋ EPCs in EPCs （NPDR vs. control, P〈0.05）. Conclusion Exogenous EPO, mediated via the EPO/EPOR system of EPCs, may alleviate the impaired vascular regeneration in NPDR, whereas it might aggravate retinal neovascularization in PDR due to a rebound of EPOR^＋ EPCs associated with ischemia.
基金Supported by the National Natural Science Foundation of China,No.81270969(to Wei Zhang)and No.81300723(to Cheng-Xiang Shan)Shanghai Science and Technology Commission,No.12ZR1439100(to Wei Zhang)
文摘AIM To examine the changes of the ghrelin/ghrelin O-acyltransferase(GOAT) axis and the mammalian target of rapamycin(m TOR) pathway in the hypothalamus after sleeve gastrectomy.METHODS A total of 30 obese type-2 diabetes Sprague-Dawley(SD) rats, 6 wk of age, fed with high-sugar and highfat fodder for 2 mo plus intraperitoneal injection of streptozotocin were randomly divided into three groups: non-operation group(S0 group, n = 10), sham operation group(Sh group, n = 10) and sleeve gastrectomy group(SG group, n = 10). Data of body mass, food intake, oral glucose tolerance test(OGTT), acylated ghrelin(AG) and total ghrelin(TG) were collected and measured at the first day(when the rats were 6 wk old), preoperative day 3 and postoperative week 8. The m RNA expression of preproghrelin, GOAT and neuropeptide Y(NPY), and protein expression of ghrelin, GOAT, GHSR and the m TOR pathway(p-Akt, p-m TOR and p-S6) were measured in the hypothalamus.RESULTS SG can significantly improve metabolic symptoms by reducing body mass and food intake. The obese rats showed lower serum TG levels and no change in AG, but the ratio of AG/TG was increased. When compared with the S0 and Sh groups, the SG group showed decreased TG(1482.03 ± 26.55, 1481.49 ± 23.30 and 1206.63 ± 52.02 ng/L, respectively, P < 0.05), but unchanged AG(153.06 ± 13.74, 155.37 ± 19.30 and 144.44 ± 16.689 ng/L, respectively, P > 0.05). As a result, the ratio of AG/TG further increased in the SG group(0.103 ± 0.009, 0.105 ± 0.013 and 0.12 ± 0.016, respectively, P < 0.05). When compared with the S0 group, SG suppressed m RNA and protein levels of preproghrelin(0.63 ± 0.12 vs 0.5 ± 0.11, P < 0.05) and GOAT(0.96 ± 0.09 vs 0.87 ± 0.08, P < 0.05), but did not change NPY m RNA expression(0.61 ± 0.04 vs 0.65 ± 0.07, P > 0.05) in the hypothalamus. The protein levels of p-Akt, p-m TOR and p-S6 were higher in the SG group, which indicated that the hypothalamic m TOR pathway was activated after SG at the postoperative week 8. CONCLUSION The reduction of ghrelin expression and activation of the m TOR pathway might have opposite effects on food intake, as SG improves obesity and T2 DM.
