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1Glutamine prevents oxidative stress in a model of portal hypertension显示文摘AIM To evaluate the protective effects of glutamine in a model of portal hypertension(PH) induced by partial portal vein ligation(PPVL).METHODS Male Wistar rats were housed in a controlled environment and were allowed access to food and water ad libitum. Twenty-four male Wistar rats were divided into four experimental groups:(1) control group(SO)-rats underwent exploratory laparotomy;(2) control + glutamine group(SO + G)-rats were subjected to laparotomy and were treated intraperitoneally with glutamine;(3) portal hypertension group(PPVL)-rats were subjected to PPVL; and(4) PPVL + glutamine group(PPVL + G)-rats were treated intraperitoneally with glutamine for seven days. Local injuries were determined by evaluating intestinal segments for oxidative stress using lipid peroxidation and the activities of glutathione peroxidase(GPx), endothelial nitric oxide synthase(e NOS) and inducible nitric oxide synthase(i NOS) after PPVL.RESULTS Lipid peroxidation of the membrane was increased in the animals subjected to PH(P < 0.01). However, the group that received glutamine for seven days after the PPVL procedure showed levels of lipid peroxidation similar to those of the control groups(P > 0.05). The activity of the antioxidant enzyme GTx was decreased in the gut of animals subjected to PH compared with that in the control group of animals not subjected to PH(P < 0.01). However, the group that received glutamine for seven days after the PPVL showed similar GTx activity to both the control groups not subjected to PH(P > 0.05). At least 10 random, non-overlapping images of each histological slide with 200 × magnification(44 pixel = 1 μm) were captured. The sum means of all áreas, of each group were calculated. The mean areas of e NOS staining for both of the control groups were similar. The PPVL group showed the largest area of staining for e NOS. The PPVL + G group had the second highest amount of staining, but the mean value was much lower than that of the PPVL group(P < 0.01). For i NOS, the control(SO) and control + G(SO + G) groups showed similar areas of staining. The PPVL group contained the largest area of i NOS staining, followed by the PPVL + G group; however, this area was significantly smaller than that of the group that underwent PH without glutamine(P < 0.01).CONCLUSION Treatment with glutamine prevents gut mucosal injury after PH in rats.Gilmara Pandolfo Zabot Gustavo Franco Carvalhal Norma Possa Marroni Francielli Licks Renata Minuzzo Hartmann Vinícius Duval da Silva Henrique Sarubbi Fillmann 2017World Journal of Gastroenterology2017,23,25:3
2N-acetylcysteine modulates angiogenesis and vasodilation in stomach such as DNA damage in blood of portal hypertensive rats显示文摘AIM: To evaluate the antioxidant effect of N-acetylcysteine(NAC) on the stomach of rats with portal hypertension.METHODS: Twenty-four male Wistar rats weighing ± 250 g were divided into four experimental groups(n =6 each): Sham-operated(SO),SO + NAC,partial portal vein ligation(PPVL),and PPVL + NAC. Treatment with NAC in a dose of 10 mg/kg(i.p.) diluted in 0.6 m L of saline solution was administered daily for 7 d starting 8 d after the surgery. Animals from the PPVL and SO group received saline solution(0.6 m L) for the same period of time as the PPVL + NAC and SO + NAC group. On the 15 th day the animals were anesthetized and we evaluated portal pressure by cannulating mesenteric artery. After,we removed the stomach for further analysis. We performed immunohistochemical analysis for endothelial nitric oxide synthase(e NOS),vascular endothelial growth factor(VEGF),and nitrotirosine(NTT) proteins in stomach. We also evaluated e NOS and VEGF by Western blot analysis and assessed DNA damage in blood samples by the comet assay.RESULTS: The portal hypertension group exhibited increases in portal pressure when compared to SO group(29.8 ± 1.8 vs 12.0 ± 0.3 mm Hg)(P < 0.001). The same was observed when we compared the e NOS(56.8 ± 3.7 vs 13.46 ± 2.8 pixels)(P < 0.001),VEGF(34.9 ± 4.7 vs 17.46 ± 2.6 pixels)(P < 0.05),and NTT(39.01 ± 4.0 vs 12.77 ± 2.3 pixels)(P < 0.05) expression by immunohistochemistry of the PPVL animals with the SO group. The expression of e NOS(0.39 ± 0.03 vs 0.25 ± 0.03 a.μ)(P < 0.01) and VEGF(0.38 ± 0.04 vs 0.26 ± 0.04 a.μ)(P < 0.01) were also evaluated by Western blot analysis,and we observed an increase of both proteins on PPVL animals. We also evaluated the DNA damage by comet assay,and observed an increase on damage index and damage frequency on those animals. NAC decreased portal pressure values in PPVL + NAC animals(16.46 ± 2 vs 29.8 ± 1.8 mm Hg)(P < 0.001) when compared to PPVL. The expression of e NOS(14.60 ± 4.1 vs 56.8 ± 3.7 pixels)(P < 0.001),VEGF(19.53 ± 3.2 vs 34.9 ± 4.7 pixels)(P < 0.05) and NTT(21.84 ± 0.7 vs 39.01 ± 4.0 pixels)(P < 0.05) evaluated by immunohistochemistry were also reduced in PPVL + NAC animals. Also,when evaluated by Western blot e NOS expression(0.32 ± 0.03 vs 0.39 ± 0.03 a.μ)(P < 0.05) and VEGF expression(0.31 ± 0.09 vs 0.38 ± 0.04 a.μ)(P < 0.01). Furthermore,NAC modulated DNA damage in PPVL + NAC animals.CONCLUSION: In view of these results,we believe NAC is able to protect the stomach from the alterations induced by the PPVL procedure.Francielli Licks Renata Minuzzo Hartmann Camila Marques Elizangela Schemitt Josieli Raskopf Colares Mariana do Couto Soares Juliana Reys Camila Fisher Juliana da Silva Norma Possa Marroni 2015World Journal of Gastroenterology2015,21,43:2
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