AIM: To investigate the roles of nuclear factor(NF)-κB and angiotensin Ⅱ receptor type 1(AT1R) in the pathogenesis of non-alcoholic fatty liver disease(NAFLD).METHODS: Forty-two healthy adult male SpragueDawley rats...AIM: To investigate the roles of nuclear factor(NF)-κB and angiotensin Ⅱ receptor type 1(AT1R) in the pathogenesis of non-alcoholic fatty liver disease(NAFLD).METHODS: Forty-two healthy adult male SpragueDawley rats were randomly divided into three groups:the control group(normal diet), the model group,and the intervention group(10 wk of a high-fat diet feeding, followed by an intraperitoneal injection of PDTC); 6 rats in each group were sacrificed at 6, 10,and 14 wk. After sacrifice, liver tissue was taken,paraffin sections of liver tissue specimens were prepared, hematoxylin and eosin(HE) staining was performed, and pathological changes in liver tissue(i.e., liver fibrosis) were observed by light microscopy.NF-κB expression in liver tissue was detected by immunohistochemistry, and the expression of AT1 R in the liver tissue was detected by reverse transcriptionpolymerase chain reaction(RT-PCR). The data are expressed as mean ± SD. A two-sample t test was used to compare the control group and the model group at different time points, paired t tests were used to compare the differences between the intervention group and the model group, and analysis of variance was used to compare the model group with the control group. Homogeneity of variance was analyzed with single factor analysis of variance. H variance analysis was used to compare the variance. P < 0.05 wasconsidered statistically significant.RESULTS: The NAFLD model was successful after 6wk and 10 wk. Liver fibrosis was found in four rats in the model group, but in only one rat in the intervention group at 14 wk. Liver steatosis, inflammation, and fibrosis were gradually increased throughout the model. In the intervention group, the body mass,rat liver index, serum lipid, and transaminase levels were not increased compared to the model group.In the model group, the degree of liver steatosis was increased at 6, 10, and 14 wk, and was significantly higher than in the control group(P < 0.01). In the model group, different degrees of liver cell necrosis were visible and small leaves, punctated inflammation,focal necrosis, and obvious ballooning degeneration were observed. Partial necrosis and confluent necrosis were observed. In the model group, liver inflammatory activity scores at 6, 10, and 14 wk were higher than in the control group(P < 0.01). Active inflammation in liver tissue in the intervention group was lower than in the model group(P < 0.05). HE staining showed liver fibrosis only at 14 wk in 4/6 rats in the model group and in 1/6 rats in the intervention group. NF-κB positive cells were stained yellow or ensemble yellow,and NF-κB was localized in the cytoplasm and/or nucleus. The model group showed NF-κB activation at6, 10, and 14 wk in liver cells; at the same time points,there were statistically significant differences in the control group(P < 0.01). Over time, NF-κB expression increased; this was statistically lower(P < 0.05) at14 weeks in the intervention group compared to the model group, but significantly increased(P < 0.05)compared with the control group; RT-PCR showed that AT1 R mRNA expression increased gradually in the model group; at 14 wk, the expression was significantly different compared with expression at 10 weeks as well as at 6 weeks(P < 0.05). In the model group, AT1 R mRNA expression was significantly higher than at the same time point in the control group(P <0.01).CONCLUSION: With increasing severity of NAFLD,NF-κB activity is enhanced, and the inhibition of NF-κB activity may reduce AT1 R mRNA expression in NAFLD.展开更多
Objective The study will explore effects of the autoantibodies against AT1 receptor and angiotensin Ⅱ on the refractory hypertension. Methods Seventy-seven patients (46 men and 31 women) with essential hypertension w...Objective The study will explore effects of the autoantibodies against AT1 receptor and angiotensin Ⅱ on the refractory hypertension. Methods Seventy-seven patients (46 men and 31 women) with essential hypertension were divided into groups of refractory hypertension (RH) and hypertension (HT) according to the 1999 WHO-ISH Guidelines for the Management of Hypertension. Forty normotensives (22 men) were recruited as controls. The mean age was 54. 3±13 years old in RH group, 53. 5±9 years old in HT group and 51. 2±11. 9 years old in normotensives (NT) group. The mean blood pressure was 154. 2±9. 4/98. 4± 8. 2 mmHg in RH group and 130. 1±7. 6/80. 5±6. 7 mmHg in HT group after combination drug therapy of hypertension for 4 weeks. Blood pressure in NT group was 120. 8±11. 7/76. 4 ± 7. 2 mmHg. The epitope of the 2nd extracellular loops of AT1 receptor was synthesized and used as antigens to screen the autoantibodies by ELISA. Plasma angiotensin (Ang) II were examined by a radioimmunoassay. Results The autoantibodies against AT1 receptor were positive in 18 (46. 15 %) patients with RH, in 4 (10. 5 % ) hypertension and in 3 (7. 5 % ) normotensives, P < 0. 01. Ang Ⅱwas 57. 01±52. 63 pmol/L in patients with RH. Both the autoantibodies positive and the Ang Ⅱ increasing were 4 (10. 3 % ) cases, both normal were 7 (17. 9 % ) cases, the autoantibodies positive or Ang II increasing was all of 14 (35. 9 % ) cases (x2 = 0. 09, P>0. 05) . There was no relationship between the autoantibodies against AT1 receptor and the angiotensin Ⅱ in refractory hypertension. Conclusion The autoantibodies against AT1 receptor and Ang Ⅱ might be two independent factors in developing of refractory hypertension. The findings suggest that AT1 receptor an-tagnist used in the treatment of refractory hypertension might have an important value.展开更多
基金Supported by grants from the Science and Technology Department of Sichuan Province,No.2011SZ0094
文摘AIM: To investigate the roles of nuclear factor(NF)-κB and angiotensin Ⅱ receptor type 1(AT1R) in the pathogenesis of non-alcoholic fatty liver disease(NAFLD).METHODS: Forty-two healthy adult male SpragueDawley rats were randomly divided into three groups:the control group(normal diet), the model group,and the intervention group(10 wk of a high-fat diet feeding, followed by an intraperitoneal injection of PDTC); 6 rats in each group were sacrificed at 6, 10,and 14 wk. After sacrifice, liver tissue was taken,paraffin sections of liver tissue specimens were prepared, hematoxylin and eosin(HE) staining was performed, and pathological changes in liver tissue(i.e., liver fibrosis) were observed by light microscopy.NF-κB expression in liver tissue was detected by immunohistochemistry, and the expression of AT1 R in the liver tissue was detected by reverse transcriptionpolymerase chain reaction(RT-PCR). The data are expressed as mean ± SD. A two-sample t test was used to compare the control group and the model group at different time points, paired t tests were used to compare the differences between the intervention group and the model group, and analysis of variance was used to compare the model group with the control group. Homogeneity of variance was analyzed with single factor analysis of variance. H variance analysis was used to compare the variance. P < 0.05 wasconsidered statistically significant.RESULTS: The NAFLD model was successful after 6wk and 10 wk. Liver fibrosis was found in four rats in the model group, but in only one rat in the intervention group at 14 wk. Liver steatosis, inflammation, and fibrosis were gradually increased throughout the model. In the intervention group, the body mass,rat liver index, serum lipid, and transaminase levels were not increased compared to the model group.In the model group, the degree of liver steatosis was increased at 6, 10, and 14 wk, and was significantly higher than in the control group(P < 0.01). In the model group, different degrees of liver cell necrosis were visible and small leaves, punctated inflammation,focal necrosis, and obvious ballooning degeneration were observed. Partial necrosis and confluent necrosis were observed. In the model group, liver inflammatory activity scores at 6, 10, and 14 wk were higher than in the control group(P < 0.01). Active inflammation in liver tissue in the intervention group was lower than in the model group(P < 0.05). HE staining showed liver fibrosis only at 14 wk in 4/6 rats in the model group and in 1/6 rats in the intervention group. NF-κB positive cells were stained yellow or ensemble yellow,and NF-κB was localized in the cytoplasm and/or nucleus. The model group showed NF-κB activation at6, 10, and 14 wk in liver cells; at the same time points,there were statistically significant differences in the control group(P < 0.01). Over time, NF-κB expression increased; this was statistically lower(P < 0.05) at14 weeks in the intervention group compared to the model group, but significantly increased(P < 0.05)compared with the control group; RT-PCR showed that AT1 R mRNA expression increased gradually in the model group; at 14 wk, the expression was significantly different compared with expression at 10 weeks as well as at 6 weeks(P < 0.05). In the model group, AT1 R mRNA expression was significantly higher than at the same time point in the control group(P <0.01).CONCLUSION: With increasing severity of NAFLD,NF-κB activity is enhanced, and the inhibition of NF-κB activity may reduce AT1 R mRNA expression in NAFLD.
文摘Objective The study will explore effects of the autoantibodies against AT1 receptor and angiotensin Ⅱ on the refractory hypertension. Methods Seventy-seven patients (46 men and 31 women) with essential hypertension were divided into groups of refractory hypertension (RH) and hypertension (HT) according to the 1999 WHO-ISH Guidelines for the Management of Hypertension. Forty normotensives (22 men) were recruited as controls. The mean age was 54. 3±13 years old in RH group, 53. 5±9 years old in HT group and 51. 2±11. 9 years old in normotensives (NT) group. The mean blood pressure was 154. 2±9. 4/98. 4± 8. 2 mmHg in RH group and 130. 1±7. 6/80. 5±6. 7 mmHg in HT group after combination drug therapy of hypertension for 4 weeks. Blood pressure in NT group was 120. 8±11. 7/76. 4 ± 7. 2 mmHg. The epitope of the 2nd extracellular loops of AT1 receptor was synthesized and used as antigens to screen the autoantibodies by ELISA. Plasma angiotensin (Ang) II were examined by a radioimmunoassay. Results The autoantibodies against AT1 receptor were positive in 18 (46. 15 %) patients with RH, in 4 (10. 5 % ) hypertension and in 3 (7. 5 % ) normotensives, P < 0. 01. Ang Ⅱwas 57. 01±52. 63 pmol/L in patients with RH. Both the autoantibodies positive and the Ang Ⅱ increasing were 4 (10. 3 % ) cases, both normal were 7 (17. 9 % ) cases, the autoantibodies positive or Ang II increasing was all of 14 (35. 9 % ) cases (x2 = 0. 09, P>0. 05) . There was no relationship between the autoantibodies against AT1 receptor and the angiotensin Ⅱ in refractory hypertension. Conclusion The autoantibodies against AT1 receptor and Ang Ⅱ might be two independent factors in developing of refractory hypertension. The findings suggest that AT1 receptor an-tagnist used in the treatment of refractory hypertension might have an important value.
