Effects of obacunone on renal interstitial fibrosis and ferroptosis in unilateral ureteral obstruction model mice / 中国药房

OBJECTVE To study the improvement effects of obacunone on renal interstitial fibrosis （RIF） in unilateral ureteral obstruction （UUO） model mice， and to investigate its mechanism based on ferroptosis mediated by nuclear factor erythroid 2- related factor 2（Nrf2）/glutathione peroxidase 4 （GPx4） signaling pathway. METHODS Thirty mice were randomly divided into sham operation group， model group， irbesartan group （positive control， 20 mg/kg）， obacunone low-dose and high-dose groups （10， 40 mg/kg）， with 6 mice in each group. Except for sham operation group， UUO model was established by ligation of unilateral ureter in other groups. After operation， administration groups were given intraperitoneal injection of relevant medicine， and sham operation group and model group were given intraperitoneal injection of constant volume of normal saline， once a day， for 7 consecutive days. The levels of creatinine （Cr） and blood urea nitrogen （BUN）， the content of malondialdehyde （MDA） and the activities of total superoxide dismutase （T-SOD） in serum and the concentration of Fe2+ in renal tissue were all detected. HE staining and Masson staining were performed to observe the morphology and the fibrosis of renal tissues. Immunohisto- chemical staining was used to determine expressions of the fibronectin （Fn）， α-smooth muscle actin （α-SMA）， GPx4 964083717@qq.com and Nrf2 in renal tissue. Western blot and real-time quantitative polymerase chain reaction （RT-qPCR） were used E-mail：834300205@qq.com to detect the protein and mRNA levels of Fn， α-SMA， Nrf2， GPx4 and SLC7A11 in the renal tissues. RESULTS Compared with sham operation group， serum levels of Cr and BUN， the concentration of Fe2+ in renal tissue， the protein and mRNA levels of Fn and α-SMA in model group were increased significantly （P＜0.05）， while the activity of T-SOD in serum， protein and mRNA expressions of Nrf2， GPx4， SLC7A11 in kidney tissue were significantly decreased （P＜0.05）； in the kidney tissue， the renal tubules were dilated， the collagen deposition was obvious， the fibrous bands were thicker and darker， and the renal interstitial inflammatory cells infiltrated significantly. After intervened with obacunone， the levels of above indexes （except for mRNA expression of SLC7A11 in obacunone low-dose group） in serum and renal tissue were reversed significantly （P＜0.05）， and pathological damage and collagen deposition of kidney tissue were alleviated. CONCLUSIONS Obacunone can improve renal interstitial fibrosis of UUO model mice， the mechanism of which may be associated with activating the Nrf2/GPx4 pathway and then inhibiting ferroptosis to relieve RIF in UUO model mice.

Effects of propiconazole on physiological and biochemical properties of Panax notoginseng and dietary risk assessment / 中国中药杂志

To study the residue and dietary risk of propiconazole in Panax notoginseng and the effects on physiological and bioche-mical properties of P. notoginseng, we conducted foliar spraying of propiconazole on P. notoginseng in pot experiments. The physiolo-gical and biochemical properties studied included leaf damage, osmoregulatory substance content, antioxidant enzyme system, non-enzymatic system, and saponin content in the main root. The results showed that at the same application concentration, the residual amount of propiconazole in each part of P. notoginseng increased with the increase in the times of application and decreased with the extension of harvest interval. After one-time application of propiconazole according to the recommended dose(132 g·hm~(-2)) for P. ginseng, the half-life was 11.37-13.67 days. After 1-2 times of application in P. notoginseng, propiconazole had a low risk of dietary intake and safety threat to the population. The propiconazole treatment at the recommended concentration and above significantly increased the malondialdehyde(MDA) content, relative conductivity, and osmoregulatory substances and caused the accumulation of reactive oxygen species in P. notoginseng leaves. The propiconazole treatment at half(66 g·hm~(-2)) of the recommended dose for P. ginseng significantly increased the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT) in P. notoginseng leaves. The propiconazole treatment at 132 g·hm~(-2) above inhibited the activities of glutathione reductase(GR) and glutathione S-transferase(GST), thereby reducing glutathione(GSH) content. Proconazole treatment changed the proportion of 5 main saponins in the main root of P. notoginseng. The treatment with 66 g·hm~(-2) propiconazole promoted the accumulation of saponins, while that with 132 g·hm~(-2) and above propiconazole significantly inhibited the accumulation of saponins. In summary, using propiconazole at 132 g·hm~(-2) to prevent and treat P. notoginseng diseases will cause stress on P. notoginseng, while propiconazole treatment at 66 g·hm~(-2) will not cause stress on P. notoginseng but promote the accumulation of saponins. The effect of propiconazole on P. notoginseng diseases remains to be studied.

Meta-analysis of the Efficacy and Safety of Prophylactic Use of Low-dose Aspirin in Patients with Chronic Renal Disease / 中国药房

OBJECTIVE：To evaluate the efficacy and safety of prophylactic use of low-dose aspirin in patients with chronic renal disease ，and to provide reference for evidence-based reference for rational use in the clinic. METHODS ：Retrieved from PubMed，Embase，Cochrane Library ，CNKI，VIP，Wanfang database ，RCTs about prophylactic use aspirin 75-150 mg/d（aspirin group）versus no aspirin and other antiplatelet drugs or placebo （control group ）were collected from inception to May 14th，2019. Relevant data were extracted. After quality evaluation with bias risk assessment tool recommended by Cochrane system evaluator manual 5.1.0，Meta-analysis of the incidence of cardiovascular events ，renal events and bleeding events in patients with chronic renal disease was performed by using Rev Man 5.3 software. RESULTS ：A total of 5 RCTs were included ，involving 4 728 patients；among them ，there were 2 392 persons in aspirin group and 2 390 persons in control group. Results of Meta-analysis showed that there was no statistical significance in the incidence of cardiovascular events [OR ＝0.59，95％CI（0.13，1.12），P＝0.11] and the incidence of renal events [OR ＝0.42，95％CI（0.08，2.23），P＝0.31] between aspirin group and control group. The incidence of bleeding events [OR ＝2.12，95％CI（1.23，3.66），P＝0.007] in aspirin group was significantly higher than control group. After exculsion of two heterogeneity literatures ，the incidence of cardiovascular events [OR ＝0.27，95％CI（0.13，0.55），P＝0.000 3] in aspirin group was significantly lower than control group. CONCLUSIONS ：Prophylactic use of low-dose aspirin can prevent cardiovascular events in patients with chronic renal disease to certain extent. The low-dose aspirin should be used carefully to prevent cardiovascular events in chronic renal disease patients with high risk of bleeding.