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The Effect of Yi Qi Yang Yin Fang Intervention on Glomerular Filtration Barrier in Adrimacycin-induced Nephropathy Rats

Author: ZhuZhi
Tutor: YuJian；XuHong；ShiZuoMin
School: Fudan University
Course: Pediatrics
Keywords: Yiqiyangyin party Adriamycin Proteinuria Heparanase nephrin
CLC: R285
Type: Master's thesis
Year: 2009
Downloads: 96
Quote: 1
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Abstract

Background primary nephrotic syndrome (PNS) is a common disease of childhood, as the main pathological type of minimal change nephrotic syndrome (MCNS), accounting for about 80%. Although the majority of children with glucocorticoid treatment effect satisfaction, but there is still a small part of the children with resistance or frequent recurrence of hormone therapy may even develop into chronic renal failure or death. In view of this, has been seeking both to improve the corticosteroid treatment, but also to reduce the hormonal side effects of new drugs and new methods. Clinical Over the years, the Chinese medicine in the treatment of children with kidney disease (including nephrotic syndrome) has made some progress. Despite years of Chinese medicine treatment of children with primary nephrotic syndrome were many, but so far in the medical treatment of the disease mechanism remains unclear. In recent years, researchers around the glomerular filtration barrier dysfunction, especially podocyte injury, depth discussion of a variety of factors involved in proteinuria. The integrity of the glomerular filtration barrier determines its selective permeability of protein. Heparan sulfate in the glomerular basement membrane (heparan sulfate, HS) filtration membrane to maintain charge barrier plays a key role. Heparanase endoglycosidase (heparanase, HPA) for β-D-within selective degradation of the glomerular basement membrane HS side chains play an important role in the mechanism of proteinuria. Similarly, nephrin as an important component of the podocyte hole diaphragm (slit diaphragm, SD) participation constitutes a the filtration membrane mechanical barrier, previous studies have shown that the occurrence of proteinuria with nephrotic syndrome and other kidney diseases closely related. Reinforcing qi nourishing our hospital in recent years, commonly used to treat children nephropathy Agreement prescription achieved a certain effect. This study was minimal change nephrotic syndrome animal model, the HPA and nephrin expression in rat kidney and changes in protein and gene level observational study to explore The Effect of the rats with adriamycin glomerular filtration barrier and its mechanism. The first part of The Effect of the rats with adriamycin purpose 24h urine protein excretion in rats observe the Yiqiyangyin side of adriamycin, changes in the biochemical markers of renal pathology, to study the benefits gas Nourishing Yin adriamycin. (1) establishment of animal models of rats with adriamycin. Male Sprague-Dawley (SD) rats, a total of 30, were randomly divided into five groups, each group of six, divided into normal control group, model group and the intervention group Yiqiyangyin party group, the intervention group the hormone group and intervention group hormone group Yiqiyangyin. Body weight 110-130g. Given the disposable tail vein injection of doxorubicin hydrochloride 5mg/kg; experimental group and control group was given intravenous injection of normal saline. Doxorubicin injection after 7 days, 14 days, 21 days and 28 days, respectively, collected 24-hour urine, the experimental group and the control group of rats were sacrificed on day 28. (2) conventional biochemical methods rats 24 hours urinary protein excretion and blood lipids, renal and other biochemical markers; pathological changes of light microscopy and electron microscopy of rat kidney. (3) The application SPSS13.0 statistical software to analyze all measurement data were expressed as mean ± standard deviation ((?) ± s) said. Groups were compared using One-Way ANOVA single-factor analysis of variance, the groups were compared using LSD test. Results (1) minimal change nephrotic syndrome animal model: the first 14 days after the injection of doxorubicin massive proteinuria (330.4 ± 198.6, P lt; 0.01), serum albumin decreased significantly (9.55 ± 3.90, lt ; 0.01), total cholesterol (1.63 ± 0.44, P lt; 0.01), and triglycerides (1.35 ± 0.11, P lt; 0.05) was significantly higher, above the indicators are in the first 28 days reached a peak. The kidney tissue electron microscopy shows experimental rats doxorubicin injection 28 natural feet protruding from widely fusion. (2) the comparison of the model group and the intervention group: intervention after 28 days party group, hormone group and Yiqiyangyin of of party hormone group Yiqiyangyin proteinuria excretion decreased serum albumin elevated cholesterol and triglycerides reduced, especially in the hormone group intervention group Yiqiyangyin party is the most obvious. (3) histomorphometric study: kidney tissue electron microscopy showed that 28 days after each intervention group doxorubicin injection podocyte foot processes partial fusion compared with the model group were light,, especially Yiqiyangyin square hormone group most Obviously, no obvious fusion of foot processes. Summary Yiqiyangyin party may alleviate the rat model of podocyte foot processes damage, reduce the excretion of urinary protein in rats with adriamycin, especially Yiqiyangyin protective effect of the hormone group is more significant. The second part of The Effect of the rat kidney of heparanase and podocyte nephrin protein purpose of study groups of rats with adriamycin renal tissue HPAmRNA expression of HPA concentration in the urine and kidney tissue nephrin mRNA The Effect of the rat kidney basement membrane and podocyte molecules nephrin protein expression. Method (1) study using animal models (rats with adriamycin) in the first part of the establishment of minimal change nephrotic syndrome, the grouping situation and drawn time with the first part. (2) real-time PCR method to detect the expression of each group 28 days after the kidney tissue HPAmRNA; using enzyme-linked immunosorbent assay method (ELISA) to detect HPA concentration in rat urine. Immunohistochemical staining, semi-quantitative and location detection nephrin protein expression; immunohistochemical image analysis using the Motie image3.2 image analysis software. (3) The application SPSS13.0 statistical software to analyze all the measurement data to mean ± standard deviation ((?) ± s) said. Groups were compared using One-Way ANOVA single-factor analysis of variance, the groups were compared using LSD test. The correlation of the analysis of the the HPA changes and proteinuria Pearson method. Results (1) experiment after 28 days, the model group rat kidney tissue HPAmRNA expression of (4.55 ± 0.38), significantly higher than the normal control group the kidney tissue HPAmRNA expression (1.50 ± 0.79), the two groups have a significant statistical significance (P lt; 0.001 ); while the other group, reinforcing qi nourishing group (3.56 ± 0.18) and Yiqiyangyin hormone group (3.13 ± 0.81) compared with the model group HPAmRNA express less significant (P lt; 0.05) which, especially the hormone group Yiqiyangyin reduction is the most significant (3.13 ± 0.81). And HPA expression in the kidney and 24h urine protein was significantly positively correlated (r = 0.708, P lt; 0.005). (2) experiment after 28 days, the model rats urine HPA concentration is higher than the normal group, a statistically significant (P lt; 0.05); while the other three groups the intervention group, HPA concentration in urine were lower than the model group, high in the normal group, but no significant difference. Nephrin mRNA levels in kidney tissue expression of (3): Compared with the control group (0.93 ± 0.07), model group, renal nephrin mRNA (1.04 ± 0.11) expression is elevated, there is a significant difference (P lt; 0.05). While the party group Yiqiyangyin, the hormone group and Yiqiyangyin party hormone group expression decreased in varying degrees, were close to the normal group (0.96 ± 0.11,0.92 ± 0.02 and 0.91 ± 0.01) expression, especially in the hormone group , Yiqiyangyin hormone group decreased significantly, there is a statistically significant (P lt; 0.05). (4) the renal tissue the nephrin average areal density than the opposite (ie, the percentage of the total area of ??nephrin protein expression area vision) expression results. Compared with the normal control group (23.77 ± 4.50), model group kidney the nephrin average surface density than decreased significantly (15.1 ± 1.42, P lt; 0.05) and statistically significant. And other interventions in each group the nephrin average surface density than with the model group were higher (16.96 ± 1.00,18.49 ± 1.60 and 19.90 ± 3.30); significant addition to the hormone group Yiqiyangyin increases ( P lt; 0.05), the other two groups was not statistically significant. (5) glomerular nephrin protein average surface density than with rats 24h urine protein between a negative correlation (r = -0.66, P lt; 0.05). Summary (1) Results Show the hormone group Yiqiyangyin party group, hormone group Yiqiyangyin, can affect kidney HPA expression that the Yiqiyangyin party may by reducing kidney HPA expression, in order to protect the glomerular filtration barrier GBM's integrity in order to achieve lower proteinuria. (2) At the same time, the results also show that Nephrin and proteinuria occurred there is a close relationship; simultaneously the hormone group the Yiqiyangyin party group, hormone group Yiqiyangyin, can affect kidney nephrin expression, and Qi Yang The female hormone group the most significant; This suggests that the mechanism to reduce proteinuria Yiqiyangyin square one, may be related to the Regulation of renal nephrin expression. Conclusion 1. Yiqiyangyin party can alleviate a rat model of podocyte foot processes damage, reduce the adriamycin rat urinary protein excretion, the hormone group Yiqiyangyin protective effect was more significant. 2. Side of Yiqiyangyin may inhibit kidney HPA, thereby protecting the GBM integrity, maintain the charge and mechanical filtration membrane barrier, final proteinuria minimize. 3 party group of Yiqiyangyin may regulate nephrin protein expression in podocytes SD, to maintain protection of the glomerular filtration barrier to reduce the occurrence and development of proteinuria. And studies have shown that hormone combined with the effect of Yiqiyangyin party more significant than the the side and hormones of Yiqiyangyin alone; This is also for clinical use both in combination provides a theoretical basis for the treatment of NS.

The Effect of Yi Qi Yang Yin Fang Intervention on Glomerular Filtration Barrier in Adrimacycin-induced Nephropathy Rats

Abstract

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