Objective To study the effect of fasudil on inhibiting the Rho/ROCK signaling pathway under high glucose in human mesangial cells (HMCs) inflammation and fibrosis. Methods Synchronized HMCs were divided into following groups: (1) Normal glucose control group ( NG, 5. 5 mmol/L glucose) ;(2) High glucose group (HG, 30 mmol/L glucose) ; (3) Mannitol group (Man, 5.5 mmol/L glucose + 24. 5 mmol/L mannitol) ; (4) High glucose + fasudil group ( HG + F, the concentrations of fasudil were 25 ,50 and 100 μmol/L, respectively). Collect the supernatant and cells at 0, 12, 24, 36, 48 and 72 h respectively, and determine the concentration changes of the RhoA, ROCK- Ⅰ, connective tissue growth factor (CTGF)mRNA with real-time PCR method in the cells, then used the ELISA method to check the protein content of the fibronectin ( FN) , CTGF, TNFα in the supernatant. Results ( 1) RhoA, ROCK- Ⅰand CTGF mRNA of the HMCs cultured under the high glucose expressed significantly higher than those in the normal group, and there was certain time-dependence. Besides, there was no statistic significance by comparing Man and NG. (2) Under the high glucose situation, after the fasudil pretreatment with different concentrations and 24 h or 48 h culture with high glucose, RhoA, ROCK- Ⅰ , CTGF mRNA expression was significantly decreased in HG + F, compared with HG, and there was certain concentration-dependence. (3) High glucose increased the FN, CTGF, TNFα protein secretion of HMCs in a time-dependent manner, but normal glucose and mannitol had no such effect. (4) After the fasudil pretreatment with different concentrations and culture with high glucose for 12, 24, 36, 48, 72 h, the FN, CTGF, TNFα protein secretion was significantly reduced compared with HG. Conclusion Fasudil can reduce the secretion of downstream inflammatory factors and cytokines by inhibiting high glucose-activated HMCs Rho/ROCK signaling pathway, and reduce the inflammation and fibrosis of HMCs. This provides a new basis for the therapeutic target in the treatment of diabetic nephropathy.

Objective:To evaluate the effect of Parkinson′s disease factor on the sedative efficacy of dexmedetomidine.Methods:The patients of either sex, aged 45-64 yr, of American Society of Anesthesiologists Physical Status classification Ⅱor Ⅲ, with body mass index of 18.5-30.0 kg/m 2, undergoing non-intracranial space-occupying lesions in neurosurgery, were selected.Patients were divided into control group (group C) and Parkinson′s disease group (group P) according to whether they had Parkinson′s disease or not.The ED 50 of dexmedetomidine was determined by using the Dixon′s up-and-down method.The initial dose of dexmedetomidine was 0.5 μg/kg in both groups, and each time the concentration increased/decreased by 0.05 μg/kg in the next patient, which was repeated until 7th independent crossover pair (loss of consciousness) appeared, and then the test was ended.The ED 50 and 95% confidence interval of dexmedetomidine inducing loss of consciousness were calculated using the probit test in a Logistic regression model.Hypertension, hypotension, bradycardia and nausea and vomiting were recorded. Results:Compared with group C, the ED 50 of dexmedetomidine inducing loss of consciousness was significantly increased in group P ( P<0.05), and no significant change was found in the incidence of adverse reactions in group P ( P>0.05). Conclusions:Parkinson′s disease factor can decrease the sedative efficacy of dexmedetomidine.