AIM: To investigate the role of oxidative injury and the effect of exogenous melatonin administration on liver damage induced by bile duct ligation (BDL), and second, to evaluate the role of nitric oxide (NO), a free ...AIM: To investigate the role of oxidative injury and the effect of exogenous melatonin administration on liver damage induced by bile duct ligation (BDL), and second, to evaluate the role of nitric oxide (NO), a free oxygen radical, in oxidative injury. METHODS: Thirty-two Sprague-Dawley rats were assigned to four groups: sham operation (SO), BDL, BDL+melatonin, and BDL+vehicle. Cholestasis was achieved by double ligature of the common bile duct. Melatonin was injected intraperitoneally 500 μg/(kg·d) for 8 d. Hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides, measured as malondialdehyde (MDA), and reduced GSH. Total nitrite (NOx) concentrations were determined in hepatic homogenates. Histopathological examination was performed using a histological scoring system. RESULTS: The histopathological changes including portal inflammation, necrosis,apoptosis, focal inflammation and fibrosis were severe in the BDL and BDL+vehicle groups. There were numerous large areas of coagulation necrosis. Histological Activity Index scores of these groups were significantly higher than that of the SO group. Treatment with melatonin reduced these alterations significantly. The degree of necro-inflammation and fibrosis showed significant difference between the BDL and BDL+melatonin groups. BDL was accompanied by a significant increase in MDA and NOx, and a significant decrease in GSH levels. Mean±SE values of MDA, GSH and NOx levels of SO group were 147.47±6.69, 0.88±0.33 μmol/g and 180.70±6.58 nm/g, respectively. The values of BDL group were 200.14±21.30, 0.65±0.02 μmol/g, and 400.46±48.89 nm/g, respectively, whereas the values of BDL+melatonin group were 115.93±6.8,0.74±0.02 μmol/g, and 290.38±32.32 nm/g, respectively. Melatonin treatment was associated with a significant recovery of MDA, GSH and NOx levels. CONCLUSION: We have concluded that oxidative stress is associated with the pathogenesis of cholestatic liver damage and NO contributes to oxidative damage. Melatonin, even at low dose, is an efficient agent in reducing negative parameters of cholestasis.展开更多
Objective： To explore the feasibility of transfecting cytidine deaminase （CD） gene into mouse bone marrow cells in order to observe the drug resistance of high dose Ara-C and improve the tolerance of myelosuppressi...Objective： To explore the feasibility of transfecting cytidine deaminase （CD） gene into mouse bone marrow cells in order to observe the drug resistance of high dose Ara-C and improve the tolerance of myelosuppression following combination chemotherapy. Methods： Human cytidine deaminase gene was transfected into mice bone marrow cells by retroviral vector. Resistant colony-forming unit granulocyte-macrophage （CFU-GM） assay was performed after the transfected mice bone marrow cells treated by the Ara-C. DNA was extracted from mice bone marrow cells. The drug resistant gene in mice bone marrow cells after transfection was detected by PCR. Results： Bone marrow cells of the donor mice cultured with the retroviral producer cells showed the drug resistant colonies and resistance to Ara-C, so did accept mice transplanted with the CD gene （CFU-GM of donor mice was 52%, χ^2 = 124.62, P 〈 0.01; accept mice was 54%, χ^2 = 126.26, P 〈 0.01, both compared with the contrast group）. The animal survival rate was significantly higher in gene transfected group than that of the control （χ^2= 7.42, P 〈 0.01）. CD gene of transfected bone marrow cells was confirmed by PCR. Conclusion： CD gene can be transfected into bone marrow cells of mice efficiently and increase the drug resistance to Ara-C.展开更多
Freeze drying has a deleterious effect on the viability of microorganisms. In front of this difficulty, the present study adopts response surface methodology to optimize the chemical compositions of protective agents ...Freeze drying has a deleterious effect on the viability of microorganisms. In front of this difficulty, the present study adopts response surface methodology to optimize the chemical compositions of protective agents to seek for maximum viability of Bifidobacterium longum BIOMA 5920 during freeze-drying. Through the compara- tive analysis of single protectant, the complex protective agents show better effect on the Bifidobacterium viability. Human-like collagen (HLC), trehalose and glycerol are confirmed as significant factors by Box-Behnken Design. The optimized formula for these three variables is tested as follows: HLC 1.23%, trehalose 11.50% and glycerol 4.65%. Under this formula, the viability is 88.23%, 39.67% higher in comparison to the control. The viable count is 1.07×10 9 cfu·g-1 , greatly exceeding the minimum viable count requirement (10 6 cfu·g-1 ).展开更多
Objective： To evaluate the renoprotection effects of non-steroidal anti-inflammatory drugs （NSAIDs） in renal ischemia-reperfusion injury （IRI） and the cyclooxygenase （COX）-1/2 blockade association by indomethac...Objective： To evaluate the renoprotection effects of non-steroidal anti-inflammatory drugs （NSAIDs） in renal ischemia-reperfusion injury （IRI） and the cyclooxygenase （COX）-1/2 blockade association by indomethacin （IMT） in the mice model. Methods： After the left renal pedicle of mice was clamped, IMT was administrated by intraperitoneal injection with four doses： 1, 3, 5, and 7 mg/kg. Blood and kidney samples were collected 24 h after IRI. The renal functions were assayed by the cytokines and serum creatinine （SCr） using enzyme-linked immunosorbent assay （ELISA） kits. Kidney samples were analyzed by hematoxylin and eosin （H＆E） and immunohistochemistry stainings. Results： The mice administered with 5 mg/kg IMT had a marked reduction in SCr and significantly less tubular damage The tumor necrosis factor a （TNF-α） activity in renal homogenates and interleukin 6 （IL-6） activity in serum had a marked reduction at doses of 5 and 7 mg/kg IMT. The administration of 3 and 5 mg/kg IMT had a marked reduction in the ratio of thromboxane B2 to 6-keto-prostaglandin F1α. COX-1 and COX-2 stainings were weaker in 5 mg/kg IMT groups than that in the other groups. Conclusions： There was a dose response in the IMT function of renal IRI in mice, and IMT had a protective effect in a certain dose range. The effect of IMT on mice IRI was related to COX-1/2 blockades.展开更多
文摘AIM: To investigate the role of oxidative injury and the effect of exogenous melatonin administration on liver damage induced by bile duct ligation (BDL), and second, to evaluate the role of nitric oxide (NO), a free oxygen radical, in oxidative injury. METHODS: Thirty-two Sprague-Dawley rats were assigned to four groups: sham operation (SO), BDL, BDL+melatonin, and BDL+vehicle. Cholestasis was achieved by double ligature of the common bile duct. Melatonin was injected intraperitoneally 500 μg/(kg·d) for 8 d. Hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides, measured as malondialdehyde (MDA), and reduced GSH. Total nitrite (NOx) concentrations were determined in hepatic homogenates. Histopathological examination was performed using a histological scoring system. RESULTS: The histopathological changes including portal inflammation, necrosis,apoptosis, focal inflammation and fibrosis were severe in the BDL and BDL+vehicle groups. There were numerous large areas of coagulation necrosis. Histological Activity Index scores of these groups were significantly higher than that of the SO group. Treatment with melatonin reduced these alterations significantly. The degree of necro-inflammation and fibrosis showed significant difference between the BDL and BDL+melatonin groups. BDL was accompanied by a significant increase in MDA and NOx, and a significant decrease in GSH levels. Mean±SE values of MDA, GSH and NOx levels of SO group were 147.47±6.69, 0.88±0.33 μmol/g and 180.70±6.58 nm/g, respectively. The values of BDL group were 200.14±21.30, 0.65±0.02 μmol/g, and 400.46±48.89 nm/g, respectively, whereas the values of BDL+melatonin group were 115.93±6.8,0.74±0.02 μmol/g, and 290.38±32.32 nm/g, respectively. Melatonin treatment was associated with a significant recovery of MDA, GSH and NOx levels. CONCLUSION: We have concluded that oxidative stress is associated with the pathogenesis of cholestatic liver damage and NO contributes to oxidative damage. Melatonin, even at low dose, is an efficient agent in reducing negative parameters of cholestasis.
基金Supported by a grant from the NationaI-Naturl Science Foundation of China （No. 30471678）.
文摘Objective： To explore the feasibility of transfecting cytidine deaminase （CD） gene into mouse bone marrow cells in order to observe the drug resistance of high dose Ara-C and improve the tolerance of myelosuppression following combination chemotherapy. Methods： Human cytidine deaminase gene was transfected into mice bone marrow cells by retroviral vector. Resistant colony-forming unit granulocyte-macrophage （CFU-GM） assay was performed after the transfected mice bone marrow cells treated by the Ara-C. DNA was extracted from mice bone marrow cells. The drug resistant gene in mice bone marrow cells after transfection was detected by PCR. Results： Bone marrow cells of the donor mice cultured with the retroviral producer cells showed the drug resistant colonies and resistance to Ara-C, so did accept mice transplanted with the CD gene （CFU-GM of donor mice was 52%, χ^2 = 124.62, P 〈 0.01; accept mice was 54%, χ^2 = 126.26, P 〈 0.01, both compared with the contrast group）. The animal survival rate was significantly higher in gene transfected group than that of the control （χ^2= 7.42, P 〈 0.01）. CD gene of transfected bone marrow cells was confirmed by PCR. Conclusion： CD gene can be transfected into bone marrow cells of mice efficiently and increase the drug resistance to Ara-C.
基金Supported by the National High Technology Research and Development Program of China (2007AA03Z456)the National Natural Science Foundation of China (20776119, 21076169 and 31000019)+5 种基金the Xi’an Research and Development Program(NC08005, YF07078)the Scientific Research Program of Shaanxi Provincial Department of Education,China(08JK452,08JK453,JG08181,2010JC21,2010JS107,2010JS108, 2010JK876 and 2010JS109)Shaanxi Provincial Scientific Technology Research and Development Program (2007K06-03, 2010JQ2012, SJ08B03)the Specialized Research Fund for the Doctoral Program of Higher Education of China (20096101120023, 20096101110014)NWU Graduate Innovation and Creativity Funds (08YSY17)Shaanxi Key Subject Program, China
文摘Freeze drying has a deleterious effect on the viability of microorganisms. In front of this difficulty, the present study adopts response surface methodology to optimize the chemical compositions of protective agents to seek for maximum viability of Bifidobacterium longum BIOMA 5920 during freeze-drying. Through the compara- tive analysis of single protectant, the complex protective agents show better effect on the Bifidobacterium viability. Human-like collagen (HLC), trehalose and glycerol are confirmed as significant factors by Box-Behnken Design. The optimized formula for these three variables is tested as follows: HLC 1.23%, trehalose 11.50% and glycerol 4.65%. Under this formula, the viability is 88.23%, 39.67% higher in comparison to the control. The viable count is 1.07×10 9 cfu·g-1 , greatly exceeding the minimum viable count requirement (10 6 cfu·g-1 ).
基金supported by the National Key Technology R&D Program of China(No.2011BAI10B07)the National Basic Research Program(973)of China(No.2012CB517603)the National High-Tech R&D Program(863)of China(No.2012AA02A512)
文摘Objective： To evaluate the renoprotection effects of non-steroidal anti-inflammatory drugs （NSAIDs） in renal ischemia-reperfusion injury （IRI） and the cyclooxygenase （COX）-1/2 blockade association by indomethacin （IMT） in the mice model. Methods： After the left renal pedicle of mice was clamped, IMT was administrated by intraperitoneal injection with four doses： 1, 3, 5, and 7 mg/kg. Blood and kidney samples were collected 24 h after IRI. The renal functions were assayed by the cytokines and serum creatinine （SCr） using enzyme-linked immunosorbent assay （ELISA） kits. Kidney samples were analyzed by hematoxylin and eosin （H＆E） and immunohistochemistry stainings. Results： The mice administered with 5 mg/kg IMT had a marked reduction in SCr and significantly less tubular damage The tumor necrosis factor a （TNF-α） activity in renal homogenates and interleukin 6 （IL-6） activity in serum had a marked reduction at doses of 5 and 7 mg/kg IMT. The administration of 3 and 5 mg/kg IMT had a marked reduction in the ratio of thromboxane B2 to 6-keto-prostaglandin F1α. COX-1 and COX-2 stainings were weaker in 5 mg/kg IMT groups than that in the other groups. Conclusions： There was a dose response in the IMT function of renal IRI in mice, and IMT had a protective effect in a certain dose range. The effect of IMT on mice IRI was related to COX-1/2 blockades.
