ABSTRACT
BACKGROUND: Cognitive impairment is a well-defined complication of chronic kidney disease (CKD), but the neural mechanisms are largely unknown. OBJECTIVES: The study aimed to assess white matter (WM) microstructure changes and their relationship with cognitive impairment development during CKD progression. METHODS: Diffusion tensor imaging (DTI) datasets were acquired from 38 patients with CKD (19 patients were at stage 3; 19 patients were at stage 4) and 22 healthy controls (HCs). Tract-based spatial statistics (TBSS) was implemented to assess the differences in WM integrity among the three groups. The associations between abnormal WM integrity and clinical indicators (digit symbol test scores, the type A number connection test scores, hemoglobin, serum urea, serum creatinine, serum calcium, and serum potassium levels) were also computed. RESULTS: Compared with patients with CKD at stage 3 and HCs, patients with CKD at stage 4 showed significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD) in the corpus callosum (CC), anterior thalamic radiation, inferior fronto-occipital fasciculus, and inferior longitudinal fasciculus. Correlation analysis showed that the MD in the genu of CC was negatively associated with the digit symbol test scores (r = -0.61, p = 0.01), and the FA in the left anterior thalamic radiation was positively associated with the level of serum calcium (r = 0.58, p = 0.01). CONCLUSION: Patients with non-end-stage CKD have multiple abnormalities in WM regions. DTI metrics change with the progression of CKD and are primarily associated with cognitive impairment. The reduced integrity of WM tracts may be related to a low level of blood calcium.
ABSTRACT
OBJECTIVE: To explore the protective effects and possible mechanism of lipoxin A(4)-methyl ester (LXA(4)-ME) in rats with acute pancreatitis (AP). METHODS: A total of 120 male SD rats were randomly divided into 3 groups: Sham operation (n = 40), AP (n = 40) and LXA(4)-ME (n = 40). Sham operation group received normal saline after sham operation. AP was induced by a retrograde infusion of 5% sodium taurocholate into pancreatobiliary duct. AP group received normal saline after modeling. In the LXA(4)-ME group, LXA(4)-ME was administered (87.5 µg/kg) intravenously after the onset of AP. The rats were sacrificed at 12 h and 24 h post-induction. Their serum levels of amylase were detected. The amount of ascites was calculated and histological changes of pancreas were observed. The activities of myeloperoxidase (MPO) and levels of malonaldehyde (MDA) in pancreas were determined. The mRNA levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-10, intercellular adhesion molecule (ICAM-1), E-selectin and nuclear factor (NF)-κB p65 in pancreas were measured by reverse transcription-polymerase chain reaction (RT-PCR). The expression of NF-κB p65 protein was also measured by immunohistochemistry. RESULTS: Compared with the AP group, the pathological scores of the LXA(4)-ME group improved (12 h: 8.7 ± 1.3 vs 11.3 ± 1.5, 24 h: 7.8 ± 1.1 vs 11.7 ± 0.8) and the amount of ascites was lower(12 h: (6.88 ± 1.23) ml vs (12.32 ± 1.94) ml, 24 h: (6.53 ± 0.91) ml vs (14.15 ± 1.68) ml, all P < 0.01). The serum levels of amylase in the LXA(4)-ME group were significantly lower than those in the AP group respectively at 12 h and 24 h post-operation (all P < 0.01). The activity of MPO and the level of MDA in pancreas in the LXA(4)-ME group were significantly lower than those in the AP group (all P < 0.01). The pancreatic expressions of TNF-α mRNA, IL-1ß mRNA, ICAM-1 mRNA, E-selectin mRNA and NF-κB p65 mRNA at 12 h and 24 h decreased in the LXA(4)-ME group versus the AP group at the corresponding time points (all P < 0.01)while the expression of IL-10 mRNA increased versus the AP group at the corresponding time points (all P < 0.01). Compared with that in the AP group, the pancreatic expression of NF-κB p65 protein decreased in the LXA(4)-ME group (12 h: 24.8% ± 3.0% vs 45.3% ± 3.4%, 24 h: 31.6% ± 3.0% vs 48.1% ± 4.6%, both P < 0.01). CONCLUSION: LXA(4)-ME exerts protective effects in AP rats. And its mechanism may be due to the suppression of NF-κB activation.
