ABSTRACT
Objective@#To investigate the effect and mechanism of hydroxyfasudi (HF), a specific Rho kinase inhibitor, on lipopolysaccharide(LPS)induced endothelial dysfunction.@*Methods@#A total of 24 male Sprague Dawley rats were randomly divided into control group(n=6), HF group(n=6), LPS group(n=6) and LPS + HF group(n=6) with random number table method. There was no special treatment in control group. HF (30 mg/kg) was injected intraperitoneally in HF group. LPS (1 mg/kg) were injected intravenously in LPS group. In LPS+ HF group, HF (30 mg/kg) was injected intraperitoneally, followed by intravenous LPS injection (1 mg/kg) 30 minutes later. All rats were sacrificed after 8 hours, and aortic tissue was extracted. RT-PCR was performed to detect mRNA levels of Rho-associated coiled-coil protein kinase (ROCK)1, connexin (Cx)43 and caveolin (Cav)1. The protein levers of ROCK1, Cx43 and Cav-1 were assessed by Western blot and immunohistochemical staining respectively.@*Results@#(1) RT-PCR experiments showed that mRNA levels of ROCK1(2.67±0.03 vs. 1.00±0.04), Cx43(1.73±0.03 vs. 1.00±0.08), and Cav1(1.85±0.04 vs. 1.0±0.03) in LPS group were significantly higher than in control group(all P<0.05). mRNA levels of ROCK1(0.38±0.02), Cx43(0.58±0.02), and Cav1(0.27±0.01) in LPS + HF group were significantly lower than in LPS group(all P<0.05). (2)Western blot analysis showed that protein levels of ROCK1(3.46±0.82 vs. 2.19±0.56), Cx43(0.33±0.09 vs.0.11±0.06), and Cav1(3.45±0.74 vs. 2.25±0.91) in LPS group were significantly higher than in control group(all P<0.05). Protein levels of ROCK1(1.09±0.52), Cx43(0.01±0.06), and Cav1(2.06±0.40) in LPS + HF group were significantly lower than in LPS group(all P<0.05). (3) Immunohistochemical staining showed that protein levels of ROCK1(84.1±0.9比53.7±2.9), Cx43(99.1±2.1 vs. 46.2±0.8), and Cav1(167.0±6.4 vs. 84.9±1.0) in LPS group were significantly higher than in control group(all P<0.05). Protein levels of ROCK1(30.4±0.6), Cx43(21.4±1.3), and Cav1(55.8±2.8) in LPS + HF group were significantly lower than in LPS group(all P<0.05).@*Conclusion@#HF attenuates LPS induced endothelial dysfunction probably via suppressing the expression of ROCK1, Cx43 and Cav1.
ABSTRACT
Objective To investigate the nephroprotective effects of prostaglandin E1 (PGE1) in the elderly undergoing coronary angiography or intervention. Methods161 patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) were randomly assigned to PGE1 group (n=87 cases) and control group (n=74 cases).10 μg lipo-PGE1 added to 100 ml normal saline were administered intravenously once daily for 5 days before and 2 days after the operation.The serum levels of creatinine (Scr) and cystatin C (Cys C) were measured on admission and 48 h after the procedure.Results After the procedure,the levels of Scr and Cys C were increased (P＜0.01) and creatinine clearance (Ccr) was decreased (P＜0.05) in control group than in PGE1 group.The incidence of contrast-induced acute kidney injury (CI-AKI) in control group 〔12.2％ (9/74)〕 was higher than in PGE1 group 〔3.4％(3/87)〕 (P＜0.05).The application of P(GE1 decreased CI-AKI,but high basic level of Scr and diabetes mellitus enhanced the incidence of CI-AKI by logistic regression.The serum levels of Cys C had negative correlation with Ccr (r=-0.615,P＜0.01).Conclusions Perioperative application of PGE1 has nephroprotective effects in the elderly undergoing CAG or PCI,and decreases the incidence of CI-AKI.The serum levels of Cys C is one of ideal indexes for auxiliary diagnosis of CI-AKI.