Enhancing effect of ultrasound-mediated microbubble destruction on gene delivery into rat kidney via different administration routes

Objective:To investigate the efficiency ofβ-galactosidase gene transfer into rat kidney with ultrasound-mediated microbubble destruction via different injection routes.Methods:A total of 25 Wistar rats were randomly divided into 5 groups.Four groups received a mixture of optison microbubbles(0.2 mL) and lacz plasmids(25μg) injection via renal artery,tail vein,anterior tibial muscle and renal parenchyma,respectively.The control group received a mixture of PBS (xx mL) and lacz plasmids(25μg) via renal artery.Three days after the gene transfer,ultrasound with fixed frequency and power(1 MHz,xxW) was delivered to the kidneys for 3 min.The efficiency of the gene transfer and expression was evaluated on the basis ofβ-galactosidase expression.The side effects of this method were evaluated by immunohistological method. Results:β-galactosidase expression could be observed only in tubules but not in glomeruli and interstitial area.The efficiency of renal artery group was higher than that of tail vein,anterior tibial muscle and renal parenchyma group(P【0.05).Immunohistochemical analysis revealed co-expression ofβ-galactosidase with a roximal tubule marker,megalin,which suggested that ultrasound enhanced gene transfer into the proximal tubular epithelial cells.Noβ-galactosidase expression was observed in the extrarenal organs.There were no evident pathological and biochemical changes after gene transfer.Conclusions:Ultrasound-mediated microbubble destruction can transfer gene into kidney via renal artery,tail vein,anterior tibial muscle and renal parenchyma.Compared with renal artery,administrating microbubbles via tail vein and anterior tibial muscle are more convenient and less vulnerarious.

Low testosterone levels are inversely correlated with carotid artery plaque formation in elderly women

Objective To study the relationship between serum testosterone levels and the plaque formation of the carotid artery in a population-based cohort of independently living healthy women above 60 years of age. Methods Analysis of the healthy elders from a population-based cohort study in 9 communities of Beijing. Carotid intima-media thickness and atherosclerotic plaques were determined ultrasonographically. Serum testosterone levels were measured by immunoassay. The data were analyzed with ANOVA and logistic regression analysis. Results There was an inverse correlation between testosterone and plaque formation in old females(P<0.01), while no association was found in males. Female with testosterone levels in the lowest quartile(<0.49 nmol/L) had more risk of plaque formation(OR=3.805, P<0.01) after adjusted with age and other traditional factors of atherosclerosis. Conclusion Testosterone concentrations are negatively associated with carotid artery atherosclerosis in old women in Beijing, experimental and prospective studies are needed to determine the possible therapeutic role of testosterone in atherosclerosis.

Effect of Shexiang Baoxin Pill(麝香保心丸) in Alleviating Early Hypertensive Renal Injury in Rats

Objective:To investigate the effect of Shexiang Baoxin Pill(麝香保心丸,SBP)on early hypertensive renal injury in rats and to explore the possible mechanism.Methods:Twelve-week-old spontaneous hypertensive rats(SHRs)with high-salt diet(dietary containing 8%NaCl)were randomized into the SBP group[40 mg/(kg·d)],losartan potassium group[20 mg/(kg·d)]and saline group by stratified random sampling method,12 in each group.Blood pressure and urea albumin creatinine ratio were measured.After 10 weeks,the expression levels of serum creatinine(Scr),hypersensitive C-reactive protein(hs-CRP),interleukin(IL)-1β,IL-6,tumor necrosis factorα(TNF-α),and transforming growth factorβ(TGF-β)in serum were assessed.Kidney pathology periodate-schiff staining was performed.Semi-quantitative count of macrophage infiltration was determined by immunochemistry of CD68 staining.Real-time quantitative polymerase chain reaction and Western blot were performed to examine the mRNA and protein expressions of Toll-like receptor 4(TLR4),nuclear factorκB(NF-κB),monocyte chemokine peptide(MCP-1),inducible nitric oxide synthase(iNOS),and arginase-1(Arg-1).Results:SBP did not affect the mortality of SHR(P<0.05).SBP significantly reduced the level of elevated blood pressure of SHRs,but the effect was less significantly than that of losartan potassium.SBP decreased urine protein(P<0.01)and the expression levels of IL-1β,IL-6,TNF-α,and TGF-βin serum.The 22-week-old SHRs showed mild proliferation of glomerular endothelial cells,glomerular ischemic lesions,inflammatory cell infiltration in renal tubular interstitium and arteriosclerosis.Both SBP and losartan potassium had alleviated renal pathological change,and significantly reduced the infiltration of macrophage(P<0.05,P<0.01).SBP and losartan potassium decreased the expressions of TLR4,NF-κB,MCP-1,iNOS,and Arg-1.Conclusion:SBP significantly modified the early hypertensive renal injury by reducing inflammation,and the effect was similar to losartan potassium.

Coronavirus diseases 2019 and kidney injury: a brief review based on current evidence

To the Editor:The global pandemic of coronavirus disease 2019(COVID-19)is not under control,and COVID-19 has affected1 tens of millions of people worldwide.Although the main features of COVID-19 are diffuse alveolar damage and acute respiratory failure,damage to other organs is also of concern because these patients tend to have more severe symptoms and worse prognosis.In this article,we briefly review the characteristics of kidney involvement in COVID-19 and the impact of kidney injury on prognosis of the disease,in order to better understand the COVID-19 epidemic from the perspective of a nephrologist.