Xuebijing injection protects against sepsis-induced myocardial injury by regulating apoptosis and autophagy via mediation of PI3K/AKT/mTOR signaling pathway in rats.

OBJECTIVE: Apoptosis and autophagy are significant factors of sepsis induced myocardial injury (SIMI). XBJ improves SIMI by PI3K/AKT/mTOR pathway. Present study is devised to explore the protective mechanism of XBJ in continuous treatment of SIMI caused by CLP. METHODS: Rat survival was first recorded within 7 days. Rats were randomly assigned to three groups: Sham group, CLP group, and XBJ group. The animals in each group were divided into 12 h group, 1 d, 2 d, 3 d and 5 d according to the administration time of 12 hours, 1 day, 2 days, 3 days or 5 days, respectively. Echocardiography, myocardial injury markers and H&E staining were used to detect cardiac function and injury. IL-1ß, IL-6 and TNF-α in serum were measured using ELISA kits. Cardiomyocyte apoptosis was assayed by TUNEL staining. Apoptosis and autophagy related proteins regulated by the PI3K/AKT/mTOR signaling pathway were tested using western blot. RESULTS: XBJ increased the survival rate in CLP-induced septic Rat. First of all, the results of echocardiography, H&E staining and myocardial injury markers (cTnI, CK, and LDH levels) showed that XBJ could effectively improve the myocardial injury caused by CLP with the increase of treatment time. Moreover, XBJ significantly decreased the levels of serum inflammatory cytokines IL-1ß, IL-6 and TNF-α in SIMI rats. Meanwhile, XBJ downregulated the expression of apoptosis-related proteins Bax, Cleaved-Caspase 3, Cleaved-Caspase 9, Cytochrome C and Cleaved-PARP, while upregulated the protein levels of Bcl-2 in SIMI rats. And, XBJ upregulated the expression of autophagy related protein Beclin-1 and LC3-II/LC3-I ratio in SIMI rats, whereas downregulated the expression of P62. Finally, XBJ administration downregulated the phosphorylation levels of proteins PI3K, AKT and mTOR in SIMI rats. CONCLUSIONS: Our results showed that XBJ has a good protective effect on SIMI after continuous treatment, and it was speculated that it might be through inhibiting apoptosis and promoting autophagy via, at least partially, activating PI3K/AKT/mTOR pathway in the early stage of sepsis, as well as promoting apoptosis and inhibiting autophagy via suppressing PI3K/AKT/mTOR pathway in the late stage of sepsis.

[Association of single nucleotide polymorphisms (SNPs) in leptin receptor gene with knee osteoarthritis in the Ningxia Hui population].

To investigate the association between primary knee osteoarthritis (OA) and single nucleotide polymorphism (SNP) (A668G) of leptin receptor gene (LEPR) in the Ningxia Hui population. A case-control association study has been adopted in this thesis. The polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis were performed to investigate the SNP of A668G site within LEPR from 148 patients with knee OA and 155 controls (asymptomatic and radiographically negative) with matched age and gender among Ningxia Hui population. In addition, genotypes of LEPR were verified by direct sequence analysis on PCR products. The result indicates that allele and genotype frequencies (P=0.024 and 0.008, respectively) in LEPR SNP A668G were significantly different in the knee OA patients group and control group, and in the knee OA patients group, the serum levels of leptin decreased significantly (P<0.001) and the serum levels of soluble leptin receptor increased significantly (P<0.001) compared with control group. Therefore, LEPR SNP A668G is associated with susceptibility to knee OA, which would be used as the genetic marker in predicting the risk of knee OA and would be one of the candidate genes in early prevention and control.

Association between the +104T/C polymorphism in the 5'UTR of GDF5 and susceptibility to knee osteoarthritis: a meta-analysis.

Although the +104T/C polymorphism in the 5' untranslated region (UTR) of growth differentiation factor 5 (GDF5) plays a role in the pathogenesis of knee osteoarthritis, the results have been inconsistent. In this study, we performed a meta-analysis to assess the association of +104T/C polymorphism with knee osteoarthritis. Published literature from PubMed, Google Scholar and China National Knowledge Infrastructure data was retrieved. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects models. A total of 6 case-control studies containing 2,744 patients and 4,518 controls were enrolled in this meta-analysis. Overall, a statistically significant association was found between the +104T/C polymorphism and risk of knee osteoarthritis (TT vs. CC: OR 1.68, 95% CI=1.41-2.01; TT vs. TC: OR 1.18, 95% CI=1.01­1.38; dominant model: OR 0.72, 95% CI=0.61-0.86). Taking into account the effect of ethnicity, further stratified analyses were performed. In the subgroup analysis, the same association was identified in Caucasian (TT vs. CC: OR 1.45, 95% CI=1.13-1.85) and Asian (TT vs. CC: OR 1.99, 95% CI=1.53­2.60; TT vs. TC: OR 1.33, 95% CI=1.16-1.52; dominant model: OR 0.64, 95% CI=0.56-0.72; recessive model: OR 1.77, 95% CI=1.37-2.29) populations. The meta-analysis results demonstrated that the +104T/C polymorphism in the 5'-UTR of GDF5 is associated with risk of knee osteoarthritis.