肾炎消白颗粒对阿霉素肾病大鼠足细胞裂隙膜蛋白分子Podocin基因表达的影响

目的:观察肾炎消白颗粒对阿霉素肾病大鼠足细胞裂隙膜蛋白分子Podocin mRNA表达的影响,探讨肾炎消白颗粒治疗肾小球肾炎蛋白尿的作用机制。方法:100只Wistar大鼠随机分正常对照组,模型对照组,肾炎消白颗粒高、低剂量组,洛汀新组5组。一次性尾静脉注入阿霉素(6.5 mg/kg),制备阿霉素肾病大鼠模型。分别采用肾炎消白颗粒和洛汀新进行干预,7周末处死大鼠,取大鼠右肾皮质,RTPCR法检测Podocin mRNA表达。结果:模型组大鼠Podocin mRNA表达明显下调,肾炎消白颗粒、洛汀新组大鼠Podocin mRNA表达明显上调,肾炎消白颗粒高剂量组的作用优于洛汀新组。结论:肾炎消白颗粒治疗肾小球肾炎蛋白尿的机制之一可能是上调足细胞Podocin mRNA的表达。

EFFECT OF HIGH-LIPID DIET ON GLOMERULAR MESANGIAL MATRIX IN ADRIAMYCIN-INDUCED NEPHROTIC RATS

OBJECTIVE: To determine the effect of hypercholsterolemia induced by a high-lipid diet on glomerulosclerosis. METHODS: Twenty nephrotic syndrome (NS) Wistar rats administrated adriamycin (ADR) with a single intravenous dose of 5 mg/kg body weight, were divided into the standard and high-lipid chow groups. Another 20 weight-matched non-NS rats that received a vehicle alone were grouped as control. Urinary protein excretion and serum cholesterol were assayed; image analysis and techniques of pathology, immunohistochemistry, and molecular biology were used to determine morphological changes in glomeruli and the production of glomerular mesangial matrices in different groups. RESULTS: The serum total cholesterol level was significantly higher in rats with high-lipid chow in both non-NS [(2.2 +/- 0.3) g/L vs. (0.9 +/- 0.1) g/L, P

Effect of Yiqiyangyin recipe on heparanase and nephrin in rats with adriamycin-induced nephropathy

OBJECTIVE： To discuss the mechanism of Yiqiyang- yin recipe in rats with adriamycin （ADR）-induced ne- phropathyo METHODS： We randomly divided 30 Sprague-Daw- ley rats into 5 groups： control, model, glucocorti- coid, Chinese herb, and Chinese herb plus glucocor- ticoid groups. The 24-h urine volume was collected on days 7, 14, 21, and 28 after ADR injection, and all rats were killed on day 28. We measured the 24-h levels of urinary protein, serum cholesterol, and se- rum triglycerides, and renal function of all rats by using routine biochemical methods. Pathological changes in the rat kidneys were observed under light and electron microscopes. Heparanase （HPA） mRNA expression levels were measured using re-al-time fluorescence-quantitative polymerase chain reaction. Urine levels of HPA in all groups were measured using enzyme-linked immunosor- bent assay. The expression of nephrin was detected by immunohistochemical staining and quantitative- ly analyzed using Motic image analysis 3.2 software. RESULTS： The levels of urinary protein and serum triglycerides and cholesterol in rats with ADR-in- duced nephropathy increased on day 14. The se- rum albumin levels simultaneously decreased. All the changes reached the peak on day 28. Examina- tion under the light microscope showed inflamma- tory cells and slight fibroplasia in the renal intersti- tium in the model group, but fewer inflammatory cells were observed in the intervention groups than those in the model group. Examination under the electron microscope showed extensive fusion of foot processes in ADR rats. HPA mRNA expres- sion was higher in the model group than that in the control group. The HPA mRNA levels in the in- tervention groups, especially in the Chinese herb group, and Chinese herb plus glucocorticoid group were significantly lower than the level in the model group. The HPA expression levels correlated signifi- cantly with the proteinuria level. No significant dif- ference was found in the HPA level in urine be- tween the intervention groups and the model group, whereas the model group had a higher uri- nary HPA level than the control group. Nephrin mRNA expression levels in the model group were higher than those in the control group. Nephrin mRNA expression levels were significantly lower in the intervention groups than that in the model group, especially the Chinese herb plus glucocorti- cold group. Compared with the control group, themodel group showed increased nephrin expression in the kidney. Nephrin levels in the other groups, es- pecially in the Chinese herb plus glucocorticoid group, were significantly lower than that in the model group. The nephrin levels in the kidney were negatively correlated with the proteinuria level. CONCLUSION： Yiqiyangyin recipe could attenuate foot process injury particularly in combination with a steroid reduce the development of proteinuria possibly by inhibition of HPA in the kidney, and reg- ulate the expression of nephrin in rats with ADR-in- duced nephropathy. Our study showed that treat- ment with Yiqiyangyin recipe plus glucocorticoid was better than a singular intervention, and we ex- plored the pharmacological mechanism of this combination by biochemical and molecular biologi- cal analysis to provide a basis for clinical applica- tion.

Pharmacodynamics of Yuebi Jiazhu Decoction on renal protection of adriamycin nephropathy rats

In the present study,we aimed to investigate the protective effect of Yuebi Jiazhu Decoction(YBJZD)on the kidney of adriamycin nephropathy(AN)rats.Rats were injected with adriamycin for modeling,except for the control group.After the successful establishment of the animal model,rats were randomly divided into the model group,YBJZD low-,medium-,and high-dose groups,and the positive group.The 24-h urine samples were collected.Biochemical indicators were monitored,and kidney tissues were collected for pathological analysis using light microscopy.The results showed that through 4 weeks of drug intervention,the urinary protein level was lower in the YBJZD and positive groups compared with the model group(P<0.05).Serum levels of BUN,SCr,and TG were significantly lower(P<0.01),and ALB was significantly higher(P<0.01)in the YBJZD and positive groups compared with the model group.Compared with the model group,the pathological injury of kidney tissue in the YBJZD and positive groups was significantly alleviated.These outcomes proved that YBJZD had a renal protective effect on AN rats.

Artemisinin ameliorated proteinuria in rats with adriamycin-induced nephropathy through regulating nephrin and podocin expressions

OBJECTIVE:To investigate the effects of artemisinin against proteinuria and glomerular filtration barrier damage in rats with adriamycin-induced nephropathy,and the potential mechanism underpinned the action.METHODS:Forty adriamycin rats were randomly divided into two groups with the ratio of 1︰3;the small-number group served as control group(n=10),and the rats in the large-number group were treated with adriamycin to induce nephropathy;then they were further randomly assigned into 3subgroups:benazepril group(n=10),artemisiningroup(n=10),and adriamycin group(n=10).The benazepril group and artemisinin group were treated with benazepril suspl(5.0 mg/kg daily)and artemisinin suspl(150 mg/kg daily)respectively after being modeled;those in the control group and adriamycin group were intragastrically administered an equivalent volume of distilled water every day.The treatment after model establishment lasted for a total of 4 weeks.The 24 h uric protein,blood biochemicals,renal pathological changes,renal ultrastrutural changes,Nephrin and Podocin proteins and gene expressions were measured by Coomassie brilliant blue assay,completely automatic biochemical analyzer,light microscope,electron microscopy,Western blot and reverse transcription polymerase chain reaction,respectively.RESULTS:The rats in adriamycin group showed a significant increase in 24 h uric protein excretion,serum total cholesterol(TC),triglyceride(TG),blood urea nitrogen(BUN),serum creatinine(Scr)and decrease in albumin(Alb)(P<0.05 or P<0.01).Compared with adriamycin group,artemisinin could reduce uric protein excretion,decrease the serum TC,TG elevation,increase the serum Alb level,up-regulate the expressions of Nephrin and Podocin(P<0.05 or P<0.01),but no statistical significance effects on the levels of BUN,Scr in artemisinin group(P>0.05).The renal pathological and ultrastrutural observation indicate that artemisinin could attenuate the severity of foot process effacement and fusion in the nephropathic rats.CONCLUSION:Artemisinin might have an effect on the nephropathy in rats caused by adriamycin,which may be at least partly correlated with attenu-ation of the severity of foot process effacement and fusion,up-regulation of the expressions of Nephrin and Podocin in the glomeruli in the rats.