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Objective To explore the rule of the Nrf2-ARE in renal interstitial fibrosis and the mechanism of butylphthalide on renal protective effect.Methods Seventy-two male CD-1 mice were divided into 4 groups,Sham group,UUO group,NBP group,ACEI group.The Sham group and UUO group were gavaged with physiological saline.The NBP group was gavaged with butylphthalide.The ACEI group was gavaged with benazepril.After 3,7,14 days,6 mice were executed and collection of kidney tissue.The expression of Nrf2,γ-GCS and type Ⅰ collagen were detected by immunohistochemisty,RT-PCR and Western blot.The correlation of Nrf2 and γ-GCS was assessmented by linear regression.Results The expression of type Ⅰ collagen in UUO group was increased compared with the Sham group,However,the expression of Type Ⅰ collagen in NBP group or ACEI group were reduced compared with the UUO group.Compared with Sham group,the expression of Nrf2mRNA,γ-GCSmRNA and type Ⅰ collagen mRNA in uuogroup were increased in 3,7,14 days after surgery.Compared with UUO group at 7th,14u day,the lelve of Nrf2 mRNA were apparently increased in NBP group (P＜0.05).It was a positive correlation between the Nrf2 and γ-GCS and negative correlation between the γ-GCS and Type Ⅰ collagen.Conclusion The renal protective effect of butylphthalide in the renal interstitial fibrosis was more predominant than benazepril.The roles maybe occurred through increased the expression of Nrf2 and γ-GCS and alleviated the expression of Type Ⅰ collagen in nephridial tissue.
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Objective To study on the possible mechanism of butylphthalide delaying renal fibrosis of mice with obstructive nephropathy. Methods Totally 72 male CD-1 mice of clean grade were selected and randomly assigned into 4 groups: sham operation group (Sham), model group (UUO), control group (ACEI) and treatment group (NBP). The mice in the control group (ACEI) and the treatment group (NBP) were given benazepril and butylphthalide by gavage, and the mice in sham operation group (Sham) and model group (UUO) were given normal saline by gavage. Six mice were sacrificed at the third, 7th, 14th day, respectively. The obstructive renal tissue was selected for immunohistochemical staining and western blot. Results (1)With the longer time of ureteral obstruction, the expression of Nrf-2 was gradually strengthened in time-dependent manner;(2)Compared with the model group, the levels of Nrf-2 and γ-GCS in butylphthalide group were significantly increased, and the expression of type Ⅰ collagen was decreased significantly (P < 0.05). The expression of Nrf-2 and γ-GCS in each time points was stronger than that in the benazepril group (P < 0.05). Correlation analysis showed that: there was a positive correlation between Nrf-2 and γ-GCS (r = 0.930) and a negative correlation between Nrf-2 and the expression level of type Ⅰ collagen(r = -0.859). Conclusion Butylphthalide can relieve renal interstitial injury caused by oxidative stress and delay the progress of renal interstitial fibrosis by activation of Nrf-2 pathway and up-regulated expression ofγ-GCS.
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Objective To investigate the effects of galangin on gene expressions of Nrf2 andγ-GCS in oxidative damage of A375 cell;To discuss its protective mechanism for anti-oxidative damage. Methods A375 melanoma cells were induced oxidative stress to establish oxidative damage model by 700μmol/L H2O2. The study was divided into normal group, model group, positive medicine group and high-, medium-, and low-dose galangin groups. All administration groups were given relevant medicine for cultivation. Cell viability was detected by MTT;ROS content was detected by ELISA;the gene expressions of Nrf2 andγ-GCS were detected by RT-PCR.Results Compared with normal group, cell viability decreased significantly;ROS content increased significantly;the gene expressions of Nrf2 andγ-GCS decreased significantly in the model group (P<0.05,P<0.01). Compared with model group, cell viability increased, ROS content decreased, the gene expressions of Nrf2 andγ-GCS increased significantly in all administration groups (P<0.05,P<0.01). Conclusion Galangin may activate Nrf2 signal path to realize the protective effect on A375 cellular oxidation damage through upregulating the expressions of Nrf2 andγ-GCS to promote the integration of Nrf2 and antioxidant response element and relevant regulatory enzymes.
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Objective To observe the effects of thin recipe ofBuyang Huanwu Decoction on expressions of glutathione (GSH) antioxidant system including GSH, GSH-Px andγ-GCS in the brain of focal cerebral ischemia rats;To study its mechanism of antioxidant effect.Methods Totally 120 SD rats were randomly divided into four groups according to random number table method:sham-operation group, model group,Buyang Huanwu Decoction group and thin recipe ofBuyang Huanwu Decoction group. Except for the sham-operation group, the rest groups established focal cerebral ischemia rat model by middle cerebral arterial occlusion. The treatment groups were given corresponding medicine by gavage, while the sham-operation group and model group were given the same amount of normal saline 2 h after modeling. Each group was detected after cerebral ischemia for 1 day, 3 days, and 7 days respectively. The content of GSH and the activity of GSH-Px were detected. At the same time,γ-GCS mRNA and protein levels were determined by using real time-PCR and Western blot.Results The content of GSH and the activity of GSH-Px at each time point decreased in the model group (P<0.05), compared with the corresponding sham-operation group. But the expression ofγ-GCS mRNA and protein increased, with statistical significance on day 1 (P<0.05). Compared with model group, content of GSH and GSH-Px activity levels increased differently in each treatment group, whileγ-GCS mRNA and protein expression raised, with statistical significance on day 3 (P<0.05).Conclusion The thin recipe ofBuyang Huanwu Decoction plays antioxidant effect by regulating the expression of glutathione antioxidant system GSH, GSH-Px andγ-GCS after cerebral ischemia, which may be one of its therapeutic mechanisms for cerebral ischemia.
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Objective To analyze the influence of adenovirus latent infection on gamma-glutamylcysteine systhetase(γ-GCS) in rat alveolar epithelial cells. Methods The rat alveolar epithelial cells were stably transfected with the plasmid pE1Aneo and control plasmid. Glutathione(GSH) contents, the activity of γ-GCS were detected in oxidant stress. Then the leuel of protein expression, mRNA expression, and promoter transcriptional activity of glutamate-cysteine ligase catalytic subunit(GCLC) were further detected. Results GSH contents decreased because of adenovirus E1A expression in oxidant stress. E1A repressed the expression and activity of γ-GCS, messenger RNA expression, and promoter transcriptional activity of GCLC. Conclusion Adenovirus E1A decreased the activity of γ-GCS probably by repressed promoter transcriptional activity of GCLC. As a result, GSH contents were downregulated in oxidant stress. Thus Adenovirus latent infection amplified the oxidant/antioxidant imbalance in rat alveolar epithelial cells in oxidants stress, which may be an important mechanism of COPD.