Leptin relieves ischemia/reperfusion induced acute kidney injury through inhibiting apoptosis and autophagy / 中南大学学报(医学版)

OBJECTIVES@#Acute kidney injury (AKI) can be caused by ischemia/reperfusion (I/R), nephrotoxin, and sepsis, with poor prognosis and high mortality. Leptin is a protein molecule that regulates the body's energy metabolism and reproductive activities via binding to its specific receptor. Leptin can inhibit cardiomyocyte apoptosis caused by I/R, but its effect on I/R kidney injury and the underlying mechanisms are still unclear. This study aims to investigate the effect and mechanisms of leptin on renal function, renal histopathology, apoptosis, and autophagy during acute I/R kidney injury.@*METHODS@#Healthy adult male mice were randomly divided into 4 groups: a sham+wild-type mice (ob/+) group, a sham+leptin gene-deficient mice (ob/ob) group, an I/R+ob/+ group, and an I/R+ob/ob group (n=8 per group). For sham operation, a longitudinal incision was made on the back of the mice to expose and separate the bilateral kidneys and renal arteries, and no subsequent treatment was performed. I/R treatment was ischemia for 30 min and reperfusion for 48 h. The levels of BUN and SCr were detected to evaluate renal function; HE staining was used to observe the pathological changes of renal tissue; TUNEL staining was used to observe cell apoptosis, and apoptosis-positive cells were counted; Western blotting was used to detect levels of apoptosis-related proteins (caspase 3, caspase 9), autophagy-related proteins [mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), LC3 I, LC3 II], mTOR-dependent signaling pathway proteins [phosphate and tension homology (PTEN), adenosine monophosphate-activated protein kinase (AMPK), protein kinase B (AKT), extracellular regulated protein kinase (ERK), phosphorylated PTEN (p-PTEN), phosphorylated AMPK (p-AMPK), phosphorylated AKT (p-AKT), phosphorylated ERK (p-ERK)].@*RESULTS@#There was no significant difference in the levels of BUN and SCr between the sham+ob/+ group and the sham+ob/ob group (both P>0.05). The levels of BUN and SCr in the I/R+ob/+ group were significantly higher than those in the sham+ob/+ group (both P<0.05). Compared with the mice in the sham+ob/ob group or the I/R+ob/+ group, the levels of BUN and SCr in the I/R+ob/ob group were significantly increased (all P<0.05). There was no obvious damage to the renal tubules in the sham+ob/+ group and the sham+ob/ob group. Compared with sham+ob/+ group and sham+ob/ob group, both the I/R+ob/+ group and the I/R+ob/ob group had cell damage such as brush border shedding, vacuolar degeneration, and cast formation. Compared with the I/R+ob/+ group, the renal tubules of the mice in the I/R+ob/ob group were more severely damaged. The pathological score of renal tubular injury showed that the renal tubular injury was the most serious in the I/R+ob/ob group (P<0.05). Compared with the sham+ob/+ group, the protein levels of caspase 3, caspase 9, PTEN, and LC3 II were significantly up-regulated, the ratio of LC3 II to LC3 I was significantly increased, and the protein levels of p-mTOR, p-PTEN, p-AMPK, p-AKT, and p-ERK were significantly down-regulated in the I/R+ob/+ group (all P<0.05). Compared with the sham+ob/ob group, the protein levels of caspase 3, caspase 9, PTEN, and LC3 II were significantly up-regulated, and the ratio of LC3 II to LC3 I was significantly increased, while the protein levels of p-mTOR, p-PTEN, p-AMPK, p-AKT, and p-ERK were significantly down-regulated in the I/R+ob/ob group (all P<0.05). Compared with the I/R+ob/+ group, the levels of p-mTOR, p-PTEN, p-AMPK, p-AKT were more significantly down-regulated, while the levels of caspase 3, caspase 9, PTEN, and LC3 II were more significantly up-regulated, and the ratio of LC3 II to LC3 I was more significantly increase in the I/R+ob/ob group (all P<0.05).@*CONCLUSIONS@#Renal function and tubular damage, and elevated levels of apoptosis and autophagy are observed in mice kidneys after acute I/R. Leptin might relieve I/R induced AKI by inhibiting apoptosis and autophagy that through a complex network of interactions between mTOR-dependent signaling pathways.

Types and epidemiological characteristics of influenza virus in Xi'an during 2009 to 2017 / 中华临床感染病杂志

Objective To analyze the types and epidemiological characteristics of influenza virus in Xi'an during 2009 to 2017.Methods A total of 21 856 samples of throat swabs from patients with influenza like illness ( ILI) were collected from 5 national influenza sentinel surveillance hospitals from August 2009 to December 2017.Influenza virus nucleic acid was detected by real-time fluorescence quantitative PCR and virus types were confirmed , chick-embryo cells or Madin-Darby canine kidney (MDCK) cells were used to isolate influenza virus.SPSS 18.0 software was used for data analysis.Results The positive detection rate of influenza virus was 16.19%(3 539/21 856), the seasonal influenza A virus subtypes including H1, H3, the new type H1and H7 accounted for 62.39%(2 208/3 539), influenza B virus subtypes including Victoria , Yamagata and unclassified type B accounted for 37.50%( 1 327/3 539), and the mixed influenza virus infection accounted for 0.11%(4/3 539).The positive rate of influenza virus detected in different years was significantly different ( χ2＝357.651, P ＜0.01).During January to March the major influenza A viruses accounted for 49.07%(947/1 930), influenza B viruses accounted for 50.93%(983/1 930); during October to December , the influenza A viruses accounted for 78.07%( 1 061/1 359 ), and influenza B viruses accounted for 21.93%( 298/1 359 ); there was significant difference in composition of type A virus and type B virus between different seasons ( χ2＝ 550.06, P＜0.05).The positive detection rate of influenza virus in patients with ILI of age groups 0-3 years,＞3-7 years,＞7-13 years,＞13-18 years,＞18-24 years,＞24-60 years and ＞60 years were 12.61%, 19.41%, 19.66%, 22.98%, 14.91%, 13.50% and 12.84%, respectively ( χ2＝202.52, P＜0.05).Conclusion Influenza A virus is common in Xi'an,winter and spring are the peak seasons for influenza epidemics.It is recommended for susceptible people to take influenza vaccination .

Improving the Quality of Urology Noviceship by the Application of Multimedia technique / 中华医学教育探索杂志

The teaching quality of urology clinical noviceship was restricted by strained teaching time,relative shortage of teaching resources and the lack of patients cooperation.Through establishing the urological multimedia data bank was established and applying the multimedia technique to assist traditional instruction,the urology noviceship quality was improved.

Identification of transcription factor SP-1 upregulating the expression of L-plastin in hormone-independent prostate cancer / 中国病理生理杂志

AIM: To identify the non-steroid transcription factors upregulating the expression of L-plastin in hormone-independent prostate cancer, and partly elucidate the mechanism of hormone-refractory prostate cancer. METHODS: TF SEARCH software was used to analysis the possible binding sites of transcription factors in the 3’ end of L-plastin promoter that had been identified as important part of regulation response elements. Gel shift assay and supershift assay were used to confirm the transcription factors binding the speculated response elements. PCR site-mutagenesis technique was performed to delete the binding site of transcription factor and luciferase activity assay was carried out after deletion of the binding site. RESULTS: SP-1 respond element GGTGGGGCGGGGA located at -54- -41 of L-plastin promoter was identified with the TF SEARCH software. Gel shift assay and supershift assay confirmed that SP-1 was the transcription factor binding to GGTGGGGCGGGGA. Mutant deleted the SP-1 binding-site had low-luciferase activity than that of the naive. CONCLUSION: SP-1 plays an important role in the up-regulation of L-plastin expression in hormone-independent prostate cancer.