AIM:To evaluate the protective mechanisms of piperine in the retina of mice with streptozotocin-induced diabetes.METHODS:In experiments in vitro,stimulation by chemical hypoxia was established in ARPE-19 cells.Then,th...AIM:To evaluate the protective mechanisms of piperine in the retina of mice with streptozotocin-induced diabetes.METHODS:In experiments in vitro,stimulation by chemical hypoxia was established in ARPE-19 cells.Then,the expression of hypoxia-inducible factor-1α(HIF-1α),vascular endothelial growth factor A(VEGFA),and pigment epithelium-derived factor(PEDF)was assessed at the m RNA and protein levels.In experiments in vivo,diabetes mellitus was established by intraperitoneally injecting 150 mg/kg streptozotocin once.After 3 wk of the onset of diabetes,15 mg/kg piperine was intraperitoneally injected once daily for 1 or 3 wk.Then,the retinal morphology and m RNA and protein expression were assessed.RESULTS:In hypoxia,1-100μmol/L piperine significantly decreased the expression of VEGFA m RNA and increased the expression of PEDF m RNA without affecting HIF-1αm RNA.Meanwhile,100μmol/L piperine substantially decreased the protein level of VEGFA and increased the protein level of PEDF.The HIF-1αprotein level was also hampered by piperine.In the diabetic retina of mice,the morphological damage was alleviated by piperine.Likewise,the retinal vascular leakage was substantially decreased by piperine.Further,the protein levels of HIF-1αand VEGFA were significantly reduced by piperine.Moreover,the level of the antiangiogenic factor of PEDF dramatically increased by piperine.CONCLUSION:Piperine may exert protective effects on the retina of mice with diabetes via regulating the pro-antiangiogenic homeostasis composed of HIF-1/VEGFA and PEDF.展开更多
Objective： To investigate the effects of electro-acupuncture on intracerebral hemorrhage （ICH）- induced angiogenesis and hypoxia-inducible factor-1 a （HIF-1 a） expression in rats. Me.otis： Adult male Sprague- Da...Objective： To investigate the effects of electro-acupuncture on intracerebral hemorrhage （ICH）- induced angiogenesis and hypoxia-inducible factor-1 a （HIF-1 a） expression in rats. Me.otis： Adult male Sprague- Dawley rats were randomly divided into 4 groups of 24 rats each. ICH was induced in 3 groups by stereotactic injection of collagenase type Ⅶ into the right globus pallidus; of these, one group was not further treated, the second group underwent Zusanli （ST36）-acupuncture, and the third group underwent non-acupoint acupuncture. ＇The fourth group underwent sham operations. Acupuncture was performed by stimulation with electrical needles at frequencies of 2-20 Hz for 30 min per day. Angiogenesis on days 3, 7 and 14 was assessed by double iimmunolabeling, and expression of HIF-1 α was evaluated by immunohistochemistry, quantitative real time reverse chain reaction and Westem blotting. Results： 5-Bromo-2-deoxyuddine （BrdU）labeled nuclei in cerebral endothelial cells （ECs） resided around the hematoma and the labeling peaked from 7 to 14 days （P〈0.01）. HIF-1 a positive microvessels with a dilated outline were detected in pedhematomal tissues after ICH, with the vessels extending into the clot from the surrounding area beginning on day 7. Following ICH, HIF-1 a protein levels increased （P〈0.05）, but HIF-1 a mRNA levels did not change. Electro-acupuncture at the Zusanli （ST36） acupoint increased BrdU-labeled nuclei in cerebral ECs （P〈0.05） and up-regulated the expression of HIF-1 a protein （P〈0.05）, but had little effect on the spatial distribution of HIF-1α or on HIF-1α mRNA levels. Conclusions： Electro-acupuncture treatment at the Zusanli （ST36） acupoint may accelerate ICH-induced angiogenesis by up-regulating HIF-1 a protein, and may enhance recovery following hemorrhagic cerebral injury.展开更多
基金Supported by the National Natural Science Foundation of China(No.81072221)Projects of Research and Development in Key Areas of Hunan Province(No.2017SK2020+1 种基金No.2020SK2133)the Natural Science Foundation of Hunan Province(No.2020JJ5005)。
文摘AIM:To evaluate the protective mechanisms of piperine in the retina of mice with streptozotocin-induced diabetes.METHODS:In experiments in vitro,stimulation by chemical hypoxia was established in ARPE-19 cells.Then,the expression of hypoxia-inducible factor-1α(HIF-1α),vascular endothelial growth factor A(VEGFA),and pigment epithelium-derived factor(PEDF)was assessed at the m RNA and protein levels.In experiments in vivo,diabetes mellitus was established by intraperitoneally injecting 150 mg/kg streptozotocin once.After 3 wk of the onset of diabetes,15 mg/kg piperine was intraperitoneally injected once daily for 1 or 3 wk.Then,the retinal morphology and m RNA and protein expression were assessed.RESULTS:In hypoxia,1-100μmol/L piperine significantly decreased the expression of VEGFA m RNA and increased the expression of PEDF m RNA without affecting HIF-1αm RNA.Meanwhile,100μmol/L piperine substantially decreased the protein level of VEGFA and increased the protein level of PEDF.The HIF-1αprotein level was also hampered by piperine.In the diabetic retina of mice,the morphological damage was alleviated by piperine.Likewise,the retinal vascular leakage was substantially decreased by piperine.Further,the protein levels of HIF-1αand VEGFA were significantly reduced by piperine.Moreover,the level of the antiangiogenic factor of PEDF dramatically increased by piperine.CONCLUSION:Piperine may exert protective effects on the retina of mice with diabetes via regulating the pro-antiangiogenic homeostasis composed of HIF-1/VEGFA and PEDF.
基金Supported by National Natural Science Foundation of China (No.30873221)Project for New Century Excellent Talents(No. NCET-11-0522)+1 种基金Hunan Provincial Natural Science Foundation (No.08JJ3077 and No.10JJ2023)the program of the Key State Administration of Traditional Chinese Medicine(SATCM) Lab of Chinese Gan(SATCM 2012-46)
文摘Objective： To investigate the effects of electro-acupuncture on intracerebral hemorrhage （ICH）- induced angiogenesis and hypoxia-inducible factor-1 a （HIF-1 a） expression in rats. Me.otis： Adult male Sprague- Dawley rats were randomly divided into 4 groups of 24 rats each. ICH was induced in 3 groups by stereotactic injection of collagenase type Ⅶ into the right globus pallidus; of these, one group was not further treated, the second group underwent Zusanli （ST36）-acupuncture, and the third group underwent non-acupoint acupuncture. ＇The fourth group underwent sham operations. Acupuncture was performed by stimulation with electrical needles at frequencies of 2-20 Hz for 30 min per day. Angiogenesis on days 3, 7 and 14 was assessed by double iimmunolabeling, and expression of HIF-1 α was evaluated by immunohistochemistry, quantitative real time reverse chain reaction and Westem blotting. Results： 5-Bromo-2-deoxyuddine （BrdU）labeled nuclei in cerebral endothelial cells （ECs） resided around the hematoma and the labeling peaked from 7 to 14 days （P〈0.01）. HIF-1 a positive microvessels with a dilated outline were detected in pedhematomal tissues after ICH, with the vessels extending into the clot from the surrounding area beginning on day 7. Following ICH, HIF-1 a protein levels increased （P〈0.05）, but HIF-1 a mRNA levels did not change. Electro-acupuncture at the Zusanli （ST36） acupoint increased BrdU-labeled nuclei in cerebral ECs （P〈0.05） and up-regulated the expression of HIF-1 a protein （P〈0.05）, but had little effect on the spatial distribution of HIF-1α or on HIF-1α mRNA levels. Conclusions： Electro-acupuncture treatment at the Zusanli （ST36） acupoint may accelerate ICH-induced angiogenesis by up-regulating HIF-1 a protein, and may enhance recovery following hemorrhagic cerebral injury.
