Change of hs-CRP, sVCAM-1, NT-proBNP levels in patients with pregnancy-induced hypertension after therapy with magnesium sulfate and nifedipine.

OBJECTIVE: To investigate the change of the hs-CRP, sVCAM-1, NT-proBNP levels of the patients with pregnancy-induced hypertension (PIH) syndrome. METHODS: A total of 200 patients with PIH were divided into mild, moderate and severe group, and 50 healthy pregnancy patients served as the control group. The serum sVCAM-1 levels were detected by enzyme-linked immunosorbent assay, hs-CRP were detected by immunity transmission turbidity, and NT-proBNP levels were determined by the colloidal gold method. Patients were treated with magnesium sulfate and nifedipine and the contrastive analysis was performed before and after treatment. And the pathological changes in placental of PIH patients were detected by hematoxylin-eosin staining at the same time. RESULTS: The hs-CRP, sVCAM-1, NT-proBNP levels of patients in the mild, moderate and severe PIH group were significantly higher than that in the control group (P<0.05). The hs-CRP, sVCAM-1, NT-proBNP levels in the severe group were significantly higher than the mild group and the moderate group, the difference was statistically significant (P<0.05). The hs-CRP, sVCAM-1, NT-proBNP of the moderate group were significantly higher than the mild group (P<0.05). There was a positive correlation between hs-CRP, sVCAM-1, NT-proBNP expression levels and the degree of the PIH. The expression of hs-CRP, sVCAM-1, NT-proBNP levels of the moderate and the severe group were significantly decreased (P<0.05). The number of placental villi and interstitial blood vessel in the moderate and severe PIH group were significantly less than the control group (P<0.05). CONCLUSIONS: The increased levels of serum hs-CRP, sVCAM-1, NT-proBNP may be involved in the process of vascular endothelial cell injury of the PIH, and the hs-CRP, sVCAM-1, NT-proBNP can be used as the auxiliary index for diagnosis of PIH and determination of PIH severity.

Dexamethasone inhibits the Nox-dependent ROS production via suppression of MKP-1-dependent MAPK pathways in activated microglia.

BACKGROUND: Nox-2 (also known as gp91phox), a subunit component of NADPH oxidases, generates reactive oxygen species (ROS). Nox-dependent ROS generation and nitric oxide (NO) release by microglia have been implicated in a variety of diseases in the central nervous system. Dexamethasone (Dex) has been shown to suppress the ROS production, NO release and inflammatory reaction of activated microglial cells. However, the underlying mechanisms remain unclear. RESULTS: The present study showed that the increased ROS production and NO release in activated BV-2 microglial cells by LPS were associated with increased expression of Nox-2 and iNOS. Dex suppressed the upregulation of Nox-2 and iNOS, as well as the subsequent ROS production and NO synthesis in activated BV-2 cells. This inhibition caused by Dex appeared to be mediated by upregulation of MAPK phosphatase-1 (MKP-1), which antagonizes the activity of mitogen-activated protein kinases (MAPKs). Dex induced-suppression of Nox-2 and -upregulation of MKP-1 was also evident in the activated microglia from corpus callosum of postnatal rat brains. The overexpression of MKP-1 or inhibition of MAPKs (by specific inhibitors of JNK and p38 MAPKs), were found to downregulate the expression of Nox-2 and iNOS and thereby inhibit the synthesis of ROS and NO in activated BV-2 cells. Moreover, Dex was unable to suppress the LPS-induced synthesis of ROS and NO in BV-2 cells transfected with MKP-1 siRNA. On the other hand, knockdown of Nox-2 in BV-2 cells suppressed the LPS-induced ROS production and NO release. CONCLUSION: In conclusion, it is suggested that downregulation of Nox-2 and overexpression of MKP-1 that regulate ROS and NO may form the potential therapeutic strategy for the treatment of neuroinflammation in neurodegenerative diseases.