ABSTRACT
Objective To investigate whether microRNA-34a (miR-34a) participates in lipopolysaccharide (LPS) mediated sepsis related renal function impairment via Kruppel-like factor 4 (KLF4). Methods Thirty healthy male Sprague-Dawley (SD) rats, weighing 180-200 g, were randomly divided into two groups: control group and model group, with 15 rats in each group. The SD rats from model group were injected with LPS 7.5 mg/kg to induce sepsis related renal function impairment model, the SD rats from control group were injected with normal saline. The serum creatinine concentration (SCr) and blood urine nitrogen (BUN) content was detected by multifunction biochemical analyzer; the morphological changes of renal tissue were observed by hematoxylin and eosin stain (HE) staining; the expression of miR-34a and KLF4 gene in plasma and renal tissue were detected by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR); the protein expression of KLF4 in renal tissue was detected by Western Blot; the target gene of miR-34a was verified by double luciferase reporter gene analysis. Results Compared with control group, inflammatory cell infiltration in renal tissue was increased in model group, the SCr and BUN were significantly increased [SCr (μmol/L): 142.5±10.6 vs. 46.4±5.6, BUN (mmol/L): 31.6±6.2 vs. 8.5±1.2, both P < 0.01], the gene expression of miR-34 in plasma and renal tissue were significantly increased (2 -ΔΔCt: 2.26±0.11 vs. 1.14±0.05 in plasma, 4.23±0.12 vs. 1.12±0.04 in renal tissue, both P < 0.01), the gene and protein expressions of KLF4 were significantly decreased [KLF4 gene (2 -ΔΔCt): 0.52±0.03 vs. 1.21±0.06, KLF4 protein (A value): 0.72±0.03 vs. 1.05±0.04, both P < 0.01], which indicated that kidney injury occurred in rats. Pearson correlation analysis showed that plasma miR-34a was positively correlated with SCr and BUN (r value were 0.678, 0.721, respectively, both P < 0.05). Double luciferase reporter assay confirmed that KLF4 was the target gene of miR-34a. Conclusion The miR-34a participates in LPS mediated sepsis related renal function impairment via KLF4.
ABSTRACT
OBJECTIVE:To observe effect and safety of continuous renal replacement therapy (CRRT) combined with differ ent doses of xuebijing sepsis patients with acute kidney injury (AKI).METHODS:One hundred and four patients diagnosed as sepsis complicated with AKI were collected from ICU of our hospital during Jun.2012 to Aug.2015.They were divided into small-dose group,medium-dose group,large-dose group and control group according to random number table,with 26 cases in each group.Four groups received routine treatment.Small-dose group was given Xuebijing injection 50 mL added into 0.9％ Sodium chlo ride injection (NS) 100 mL,ivgtt,bid;medium-dose group was given Xuebijing injection 100 mL added into NS 100 mL,ivgtt,bid;large-dose group was given Xuebijing injection 100 mL added into NS 100 mL,ivgtt,qid.All patients were treated for 1 week.The levels of IL-6,TNF-α and hs-CRP were observed in 4 groups before and after treatment;renal function indexes as BUN,SCr and CysC,blood coagulation function indexes as PT,APTT and Fib were also observed as well as APACHE Ⅱ score and Marshall score.The occurrence of ADR were recorded during treatment.RESULTS:Ninety-five cases meeting the criteria were finally included in the study after 9 cases withdrew from the study,and there were 23,24,25,23 cases in small-dose group,medium-dose group,large-dose group and control group,respectively.Before treatment,there was no statistical significance in above indexes among 4 groups (P＞0.05).After treatment,the serum levels of IL-6,TNF-α,CRP,PT and APTT,APACHE Ⅱ score and Marshall score in 4 groups were all decreased significantly,while the serum levels of BUN,SCr,CysC and Fib were increased significantly;the improvement of above indexes in small-dose group,medium-dose group and large-dose group were all better than in control group,and the large-dose group was significantly better than the small-dose group and medium-dose group,with statistical significance (P＜0.05).There was no statistical signifi cance in the incidence of ADR among 4 groups (P＞ 0.05).CONCLUSIONS:Large-dose xuebijing combined with CRRT can effectively inhibit inflammatory reaction in sepsis patients with AKI,improves renal function and coagulation function,and dose not increase the risk of ADR.