Protective effect of dexmedetomidine against renal injury in diabetic nephropathy rats through inhibiting NF-κB pathway.

OBJECTIVE: The aim of this study was to investigate the protective effect of dexmedetomidine (Dex) against renal injury in diabetic nephropathy (DN) rats by inhibiting the nuclear factor-κB (NF-κB) pathway. MATERIALS AND METHODS: A total of 36 Sprague-Dawley rats were randomly divided into three groups, including: normal group (n=12), model group (n=12) and Dex group (n=12). The rats underwent no treatment in normal group. In model group, the diabetes model was successfully established, and normal saline was intraperitoneally injected after operation. In Dex group, the diabetes model was established as well, and Dex was intraperitoneally injected after operation. After intervention for 2 weeks, the samples were taken for use. Blood urea nitrogen (BUN) and serum creatinine (Cr) were detected using a full-automatic biochemical analyzer. The expression of Caspase-3 was detected via immunohistochemistry. Western blotting was conducted to detect the protein expression of NF-κB. The apoptosis was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. In addition, the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were determined via enzyme-linked immunosorbent assay (ELISA). RESULTS: The levels of BUN and Cr were significantly higher in model group and Dex group than those in normal group (p<0.05). However, they were significantly lower in Dex group than those in the model group (p<0.05). Immunohistochemistry results showed that the mean optical density of Caspase-3 positive expression increase remarkably in model group and Dex group when compared with normal group (p<0.05). However, it significantly declined in Dex group when compared with the model group (p<0.05). The results of Western blotting revealed that model group and Dex group exhibited evidently higher relative protein expression of NF-κB than normal group (p<0.05). However, Dex group displayed notably lower relative protein expression of NF-κB than model group (p<0.05). TUNEL assay demonstrated that the apoptosis rate increased significantly in the model group and Dex group when compared with normal group (p<0.05). However, it remarkably declined in Dex group in comparison with the model group (p<0.05). Finally, ELISA assay indicated that model group and Dex group had markedly higher levels of IL-6 and TNF-α than normal group (p<0.05). However, the levels of IL-6 and TNF-α were significantly lower in Dex group than model group (p<0.05). CONCLUSIONS: Dex inhibits inflammation and apoptosis by suppressing the NF-κB signaling pathway, thereby exerting a protective effect against renal injury in DN rats.

[Risk factors for short-term outcome of patients with HBV-related acute-on-chronic liver failure].

OBJECTIVE: To investigate the risk factors for the short-term outcome of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF), and to establish a risk model for predicting the short-term outcome of these patients. METHODS: A total of 338 patients with HBV-related ACLF who were admitted to 30 Lod hospital of PLA hospital from January 2010 to January 2014 were enrolled, and a prospective clinical follow-up was performed for them. Multivariate logistic regression was used to determine the risk factors for short-term (12 weeks) outcome, the predictive model with logistic regression equation was established, and the predictive value of this model was evaluated. RESULTS: The multivariate logistic regression analysis showed that age, a family history of hepatitis B, hepatic encephalopathy (HE), hepatorenal syndrome (HRS), white blood cell (WBC), platelet (PLT), international normalized ratio (INR), total bilirubin (TBil), total bile acid (TBA), creatinine, Na, HBV DNA, and HBeAg were the independent risk factors for the short-term outcome of these patients. Logistic(p) = -4.466 + 1.192 age + 1.631 family history of hepatitis B + 1.091 HE + 1.631 HRS + 1.208 WBC -1.487 PLT + 1.092 INR + 1.446 TBil + 1.608 TBA -1.101 CHE + 1.279 CRE -1.713 Na + 1.032 HBV DNA + 0.833 HBeAg. The area under the receiver operating characteristic curve of the model for the prediction of short-term outcome was 0.930, the cut-off value was 3.16, the sensitivity was 0.860, and the specificity was 0.871. With the increasing scores of the equation, the mortality of patients tended to increase gradually. CONCLUSION: Age, a family history of hepatitis B, HE, HRS, WBC, PLT, INR, TBil, TBA, CHE, CRE, Na, HBV DNA, and HBeAg are the independent risk factors for the short-term outcome of patients with HBV-related ACLF. The model for predicting short-term outcome established on the basis of independent risk factors has a better clinical value in guiding clinical therapy.

Tim-3 expression on peripheral monocytes and CD3+CD16/CD56+natural killer-like T cells in patients with chronic hepatitis B.

Hepatitis B virus (HBV) infection is one of the major causes of chronic liver inflammation. Tim-3 acts as a negative regulatory molecule and plays a critical role in immune tolerance. In the current study, we investigated Tim-3 expression on peripheral monocytes and CD3+CD16/CD56+ natural killer like T (NKT-like) cells in chronic hepatitis B (CHB) patients. Peripheral blood mononuclear cells (PBMCs) were isolated from 52 CHB patients and 60 healthy controls. Tim-3+CD14+ cells and Tim-3+CD3+CD16/CD56+ cells were analyzed by flow cytometry. Results showed that expression of Tim-3 was significantly increased on both the monocytes and NKT-like cells in CHB patients than in controls (P = 0.002 and P < 0.001, respectively). Tim-3 levels on monocytes and NKT-like cells were further upregulated in patients with acute-on-chronic liver failure (ACLF). In addition, we assessed the correlation of Tim-3 expression with levels of alanine aminotransferase (ALT) and tumor necrosis factor alpha (TNF-α). Data revealed that Tim-3 expression on both monocytes and NKT-like cells was positively correlated with level of ALT (r = 0.59, P < 0.001, and r = 0.60, P < 0.001, respectively), whereas Tim-3 expression on NKT-like cells was negatively correlated with serum level of TNF-α (r = -0.54, P < 0.001) in CHB patients. Our results suggest that Tim-3 may play important roles in the pathogenesis of CHB.

Age-related changes in kallikreins-kinins system in rat corpus cavernosum.

Many factors, such as nitric oxide synthase, androgen and growth factors, can regulate the tone of corpus cavernosum (CC) smooth muscle with an age-related tendency. It has been shown that the active metabolites of kallikreins-kinins system (KKS), including bradykinin, Lys-BK and Met-Lys-BK, can also relax the CC smooth muscle significantly in vitro. Our aim was to evaluate the specific association between KKS and age in rat CC. CC and thoracic aorta were isolated from rats at postnatal weeks (PW) of 2, 8, 12, 20, 30, 40 and 60, respectively. Tissue kallikrein-I (KLKI) and kinin B2 receptor (B2R) mRNA in CC and thoracic aorta were detected by real-time polymerase chain reaction (PCR). Protein expression of KLKI and B2R were determined with immunofluorescence in situ and Western blot. Real-time PCR, immunofluorescence in situ and Western blot all demonstrated that the age-related changes in expression of KLKI were similar between the CC and thoracic aorta. It significantly increased with age from PW2 to PW30, reached the peak at PW30 and then declined gradually. However, there was no statistically significant difference among PW30, PW40 and PW60. Similarly, the expression of B2R increased gradually with age reached and remained at the peak during adult stages and no significant differences were found among PW20, PW30 and PW40; then, it decreased significantly at PW60. The changes in the expression of B2R in CC and age-matched aorta were similar except that it was significantly less than that in the aorta at PW60. The expression of KLKI and B2R changed in an age-dependent pattern in rat CC and have a tendency to decline during ageing, which is of the same tendency as reported for erection capacity in ageing males and suggests why ageing is an independent predictor of ED, to some extent.

Electron crystallographic image-processing investigation and superstructure determination for (Pb0.5Sr0.3Cu0.2)Sr2(Ca0.6Sr0.4)Cu2Oy.

An electron crystallographic image-processing technique based on the combination of high-resolution electron microscopy and electron diffraction has been developed to investigate the commensurate structural modulation in the high-Tc superconductor (Pb0.5Sr0.3Cu0.2)Sr2(Ca0.6Sr0.4)Cu2Oy. After symmetry averaging, a structure image was obtained by image deconvolution at the resolution limited by that of the electron microscope. Then phase extension was employed to enhance the image resolution up to about 1.25 A by means of the electron diffraction data corrected with an empirical method. In the final projected potential map, the occupational and/or positional modulation is clearly observed for all atoms, including oxygen. The key points of determining superstructures by the technique are studied and discussed.

[Role of afferent renal nerves in 2K2C Goldblatt hypertension].

In order to study the role of afferent renal nerves in 2K2C Goldblatt hypertension, the renal afferent nerves were selectively lesioned by bilateral T9-L2 spinal dorsal rhizotomy before clipping (internal diameter, 0.3 mm) of birenal arteries. Systolic blood pressure of the rat was measured by tail-cuff method. Concentrations of catecholamines, Ang II, and aldosterone were determined respectively by HPLC-EC and RIA, and vascular structural changes were measured by blood vessel micro-image analysis system coupled with a computer. The results showed that the concentrations of NE and E in medulla oblongata, adrenal gland and plasma, and of plasma Ang II and aldosterone as well as body weight of the rat were all significantly increased. The heart coefficient (heart wt/body wt), the media thickness, and the media thickness/lumen diameter in superior mesenteric arteries were also increased in 2K2C hypertensive rats (clipping, 6 wk) as compared with those in control rats. Bilateral rhizotomy delayed development of 2K2C hypertension and prevented above-mentioned vascular structural changes, the NE and E concentrations of medulla oblongata, adrenal gland and plasma were all decreased, hypothalamic NE and E were increased, and plasma Ang II level was not significantly changed. These results suggest that afferent renal nerves may play a partial role in the development of hypertension in 2K2C rats by activating sympathetic nervous system as a result of affecting metabolic activities of brain catecholaminergic neurons, and that high-plasma Ang II and aldosterone as well as heart hypertrophy and proliferation of vascular smooth muscle cells may also participate in the pathogenesis of hypertension in 2K2C rats.