Effects and mechanisms of total flavones of Abelmoschus manihot in improving insulin resistance and podocyte epithelial-mesenchymal transition in diabetic kidney disease based on IRS1/PI3K/Akt pathway / 中国中药杂志

This study aimed to explore the effects and mechanisms of total flavones of Abelmoschus manihot(TFA), the extracts from traditional Chinese medicine indicated for kidney diseases, on insulin resistance(IR) and podocyte epithelial-mesenchymal transition(EMT) in diabetic kidney disease(DKD), and further to reveal the scientific connotation. Thirty-two rats were randomly divided into a normal group, a model group, a TFA group, and a rosiglitazone(ROS) group. The modified DKD model was induced in rats by methods including high-fat diet feeding, unilateral nephrectomy, and streptozotocin(STZ) intraperitoneal injection. After modeling, the rats in the four groups were given double-distilled water, TFA suspension, and ROS suspension correspondingly by gavage every day. At the end of the 8th week of drug administration, all rats were sacrificed, and the samples of urine, blood, and kidney tissues were collected. The parameters and indicators related to IR and podocyte EMT in the DKD model rats were examined and observed, including the general condition, body weight(BW) and kidney weight(KW), the biochemical parameters and IR indicators, the protein expression levels of the key signaling molecules and structural molecules of slit diaphragm in the renal insulin receptor substrate(IRS) 1/phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway, foot process form and glomerular basement membrane(GBM) thickness, the expression of the marked molecules and structural molecules of slit diaphragm in podocyte EMT, and glomerular histomorphological characteristics. The results showed that for the DKD model rats, both TFA and ROS could improve the general condition, some biochemical parameters, renal appearance, and KW. The ameliorative effects of TFA and ROS were equivalent on BW, urinary albumin(UAlb)/urinary creatinine(UCr), serum creatinine(Scr), triglyceride(TG), and KW. Secondly, they could both improve IR indicators, and ROS was superior to TFA in improving fast insulin(FIN) and homeostasis model assessment of insulin resistance(HOMA-IR). Thirdly, they could both improve the protein expression levels of the key signaling molecules in the IRS1/PI3K/Akt pathway and glomerulosclerosis in varying degrees, and their ameliorative effects were similar. Finally, both could improve podocyte injury and EMT, and TFA was superior to ROS. In conclusion, this study suggested that podocyte EMT and glomerulosclerosis could be induced by IR and the decreased activation of the IRS1/PI3K/Akt pathway in the kidney in DKD. Similar to ROS, the effects of TFA in inhibiting podocyte EMT in DKD were related to inducing the activation of the IRS1/PI3K/Akt pathway and improving IR, which could be one of the scientific connotations of TFA against DKD. This study provides preliminary pharmacological evidence for the development and application of TFA in the field of diabetic complications.

The clinical efficacy and analysis of extracorporeal membrane oxygenation for adult severe acute respiratory distress syndrome / 中国基层医药

Objective To investigate the clinical experience and associated factors of extracorporeal membrane oxygenation(ECMO)for adult patients with severe acute respiratory distress syndrome(ARDS).Methods The clinical data of 22 adult patients with severe ARDS,which met the criteria for ECMO,were retrospectively collected and analyzed.The ECMO team all receiving VV-ECMO treatment (Veno-venous extracorporeal membrane oxygenation),data collection including the patients,general data,blood gas analysis,hemodynamics,mechanical ventilation parameter before and after the ECMO treatment and the auxiliary complications,etc.The control group were 14 cases of patients with severe ARDS which receiving conventional treatment;We collected the same data as the research team.Results In the research,8 patients treated with VV-ECMO,There were 5 males and 3 females,with an average age of (46.3 ± 14.1)years.Compared with the factors at the same time point in the control group,those of the ECMO group,except MAP (t =-0.872,P =0.357),Respiratory rate (t =-1.670,P =0.357),Heart rate (t =-1.973,P =0.042),PH (t =-1.432,P =0.033),PaCO2 (t =-2.564,P =0.024),PO2 (t =-4.955,P ＜ 0.001),PO2/FiO2 (t =-3.654,P ＜ 0.01),PEEP (t =-1.382,P =0.031),Pplateau (t =-2.785,P ＜ 0.01),Blood lactate (t =-2.564,P =0.024) were significantly improved after ECMO running 24 hours (all P ＜ 0.05).And also the factors such as the length of ICU stay (t =-2.452,P =0.027),the times of mechanical ventilation (t =-1.478,P =0.038),number of organ failure(t =-1.963,P =0.047),the hospital mortality rates(t =-1.970,P =0.045) and treatment costs(t =-1.667,P =0.035) between the ECMO group and the control group were significantly different (P ＜0.05).In the end,we divided the ECMO group into survival group and death group,and compare the time of Mechanical Ventilation before ECMO(P =0.031) the total time of Mechanical Ventilation(P =0.038),the time of ECMO adjutant (P =0.047),the length of ICU stay (P =0.043) and the cost of treatment (P =0.037) between the two groups;and there were also statistically significant difference (P ＜ 0.05).Conclusion ECMO can significantly improve the patients,oxygenation and respiratory physiology indexes which can not sustain under the conventional mechanical ventilation therapy and win the time for rest and repair of lung.Indexes such as age,time of mechanical ventilation before ECMO therapy,the primary cause of ARDS are the important factors influencing the efficacy of ECMO treatment in the patients with severe ARDS.