ABSTRACT
Objective:To investigate the protective function and mechanism of β-hydroxybutyrate (β-HOB) on cisplatin (CP)-induced nephrotoxicity.Methods:C57BL/6 male mice aged 10 weeks were randomly divided into the following three groups: control group (no special treatment), β- HOB+CP group (mice received intraperitoneal injection of 20 mmol/kg β-HOB for 10 days), CP group (received intraperitoneal injection of normal saline for 10 days). CP group and β-HOB+CP group were given once cisplatin (20 mg/kg) intraperitoneal injection on the 8th day in the experiment. On the 10th day, all the mice were sacrificed. Renal pathology was evaluated by HE staining; blood samples were collected for blood urea nitrogen (BUN) and serum creatinine (Scr) measurement; immunohistochemistry staining was performed to detect the protein level of Caspase3, Cleaved-caspase3, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) in renal tissues; Western blotting was used to detect the relative expression levels of p-MAPK/MAPK and p-NF-κB/NF-κB. In vitro experiment, HK-2 cells were set into three groups: control group, CP group, β-HOB+CP group, and β-HOB+CP+Sappanone A (Sap, MAPK-p38 activator) group. The expression levels of p-MAPK, p-NF-κB, Caspase3 and Cleaved-caspase3 were tested by cell immunofluorescence. The cell apoptosis and mitochondrial membrane potential (MMP) were examined by flow cytometry. DNA damage was detected by TUNEL staining. Results:In vivo experiments, the renal pathological injury score, BUN and Scr in CP group were significantly higher than those in control group (all P<0.05), while renal pathological injury score, BUN and Scr in β-HOB+CP group were lower than those in CP group (all P<0.05). The protein expression levels of p-MAPK, p-NF-κB, Caspase3 and Cleaved-caspase3 in CP group were higher than those in control group, while these indexes in β-HOB+CP group were lower than those in CP group (all P<0.05). In vitro experiments, compared with CP group, the MMP was higher in β-HOB+CP group; the ratio of cell apoptosis, the expression of Caspase3, Cleaved-caspase3, p-MAPK and p-NF-κB, and the number of TUNEL staining positive cells were significantly lower (all P<0.05). Compared with β-HOB+CP group, the MMP in β-HOB+CP+Sap group was lower; the ratio of cell apoptosis, the expression of Caspase3 and Cleaved-caspase3, and the number of TUNEL staining positive cells were significantly higher (all P<0.05). Conclusions:β-HOB can alleviate the acute renal injury induced by cisplatin, which may be related to the reduction of apoptosis and inhibition of MAPK/NF-κB pathway.
ABSTRACT
Objective To evaluate the risk clinic factors of severe community-acquired pneumonia in older adults,and to provide examples for its clinic application.Methods Sixty-four case patients who were admitted for a diagnosis of severe community-acquired pneumonia in older adults in Beijing Haidian Hospital from January 2013 to July 2015 were selected as observation group.One hundred cases patients also admitted for a diagnosis of community-acquired pneumonia were selected as control group.Within 24 h of admission,the clinical data were collected,medical history were collected,and the serum biochemistry,coagulation index fibrin degradation product,D-dimer and inflammatory factor procalcitonin were detected.The data were analyzed by univariate analysis,and logistic regression analysis was used to analyze the variables with significant difference in single factor analysis.Results Single factor analysis showed that the percentage of severe pneumonia with central nervous system disorders,severe pneumonia with aspiration,severe pneumonia with two or more comorbidities,aspiration and severe pneumonia with bedridden patient in observation group were obviously higher than the control group,the difference between two groups have remarkable statistical significance((82.21％ (53/64) vs.32％(32/100),60.93％(39/64) vs.1％(1/100),(84.37％,54/64) vs.54％(54/100),90.62％(58/ 64) vs.28％ (28/100),59.37％ (38/64) vs.11％ (11/100);P＜0.01 or P＜0.05).The mortality of observation group was higher than the control group,the difference between two groups have remarkable statistical significance(56.62％ (36/64)] vs.3％ (3/100),P=0.001).Albumin of severe pneumonia was obviously lower than the control group,the difference between two groups have remarkable statistical significance ((27.79 ±8.53) g/L vs.(33.66±9.63) g/L,P=0.011).Fibrin degradation product of severe pneumonia was obviously lower than the control group,the difference between two groups have remarkable statistical significance ((i0.98 ± ± 1.32) ng/L vs.(3.61±0.98) ng/L,P=0.002).D-dimer of severe pneumonia was obviously higher than the control group,the difference between two groups have remarkable statistical significance ((2.68± 0.56) mg/L vs.(0.42±0.12) mg/L,P=0.001).Procalcitonin of severe pneumonia was obviously higher than the control group,the difference between two groups have remarkable statistical significance ((1.63±0.32) ng/L vs.(0.13 ± ±0.21) ng/L,P =0.015).The result of multiple factors logistic regression analysis showed the aspiration,hypoproteinemia,D-dimer were severe community-acquired pneumonia in older adults's independent risks (OR =1.782,1.208,1.356,P＜0.05).Conclusion Aspiration,hypoproteinemia,D-dimer are the factors of risking suffering severe community-acquired pneumonia in older adults.D-dimer could be the detection index of severe community-acquired pneumonia in older adults.