• Applied Microscopy
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• 제28권4호
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• pp.577-590
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• 1998

Puromycin aminonucleoside (PAN) nephropathy was induced in a group of Sprague-Dawley rat by a single dose of intraperitoneal Injection to study an ultrastructural change of glomerulus. The experimental rats developed proteinuria three days after PAN injection. Electron microscopic studies of glomeruli showed the loss of epithelial foot processes, formation of cytoplasmic vacuoles, microvillous formation and increased numbers of lysosomes in the cytoplasm of podocytes. It is strongly suggested that proteinuria in PAN nephrosis may be primarily due to a glomerular epithelial lesion, leading to focal disarray of anionic sites or focal defects in the epithelial covering of the basement membrane. The loss of anionic sites in the basement membrane nay be caused by the foot process fusion and the epithelial detachment from the basement membrane.

• 대한예방한의학회지
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• 제4권1호
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• pp.104-121
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• 2000

The effects of Soohwabunchungum on rats with nephrosis induced by a single tail-intravenous injection of PAN(puromycin aminonucleoside), 2.5mg/100g of body weight was evaluated in the present study. The effects of Soohwabunchungum on PAN nephrosis was evaluated by measuring the concentrations of albumin, total protein, total lipid, cholesterol, triglyceride, creatinine, BUN(blood urea nitrogen) and uric acid in the serum the amount of protein, creatinine, glucose, occult blood and volume of the 24 hours urine and the volume of intake water, To conclude, it can be inferred that Soohwabunchungum has the effects of improving proteinuria, hypoproteinemia, hyperlipidemia in nephrotic syndrome, and relieving azotemia when nephrotic syndrome is accompanied by the acute renal failure.

• 대한한의학회지
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• 제23권1호
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• pp.156-169
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• 2002

Objectives : This experimental study was performed to prove the effect of Ikryung-Tang (yiling-tang; IRT) and Ikryung-tangkamibang (yiling-tangjiaweifang; IRT I, IRT II) on rats with nephrosis induced by a single intravenous injection of puromycin aminonucleoside (PAN). Methods : The effects of IRT, IRT I and IRT II on PAN nephrosis were evaluated by measuring the gene expression of IL-4, $IFN-{\gamma}$ and the concentrations of IgE, albumin, total protein, cholesterol, triglyceride, creatinine, and BUN in the serum and the volume & amount of protein of the 24hrs' urine. Results : In the gene expression linked T cell specialization, IRT II inhibited IL-4 and IgE but IRT and IRT I showed no significant difference compared with control group. On the other hand, IRT, IRT I and IRT II increased $IFN-{\gamma}$ compared with the control group. In the urine protein, serum albumin, total protein, BUN, and creatinine, IRT I especially showed more. significant effect than other groups. In the serum cholesterol and triglyceride, IRT II especially showed more significant effect than other groups. In the urine volume during 24 hrs, IRT especially showed more significant effect than other groups. Conclusions : According to the above results, it is suggested that IRT is effective for the treatment of edema, IRT I is effective for the treatment of hypoproteinemia and kidney dysfunction, IRT II is effective for immune modulation and the treatment of cholesteremia. Therefore IRT, IRT I and IRT II seem to be available for treating nephrosis in clinical practice.

• 대한한방부인과학회지
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• 제34권4호
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• pp.1-11
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• 2021

Objectives: Nephrotic syndrome is a kidney disorder, which is characterized by proteinuria, edema (swelling), and hyperlipidemia. Maydis Stigma (Corn silk) has been widely used in Asia as a traditional medicine and is known to have a diuretic effect and is used for the treatment of edema and indigestion. Methods: The aim of this study is to investigate the improvement effect of Maydis Stigma in treating nephrotic syndrome induced by puromycin aminonucleoside. Sprague-Dawley rats were intravenously injected with 75 mg/kg/day puromycin aminonucleoside, then treated with either Losartan or 200 mg/kg/day Maydis Stigma for seven days. Results: Maydis Stigma significantly decreased ascites and proteinuria level. Plasma levels of blood urea nitrogen (BUN) and plasma creatinine reduced significantly by Maydis Stigma. In addition, treatment with Maydis Stigma attenuated histological damage. Treatment with Maydis Stigma also restored podocin expression and reduced inflammation markers such as intracellular adhesion molecules (ICAM-1), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor alpha (TNF-α) and high-mobility group box-1 (HMGB1). Conclusions: Maydis Stigma ameliorates kidney injury in nephrotic syndrome rat models. Maydis Stigma exerts a renoprotective effect owing to its anti-inflammatory effects and reductions of ascites and proteinuria. Thus, these results indicate that Maydis Stigma is likely to be a promising agent in the treatment of nephrotic syndrome.

• Clinical and Experimental Pediatrics
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• 제55권10호
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• pp.371-376
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• 2012

Purpose: Puromycin aminonucleoside (PAN) specifically injures podocytes, leading to foot process effacement, actin cytoskeleton disorganization, and abnormal distribution of slit diaphragm proteins. p130Cas is a docking protein connecting F-actin fibers to the glomerular basement membrane (GBM) and adapter proteins in glomerular epithelial cells (GEpCs; podocytes). We investigated the changes in the p130Cas expression level in the PAN-induced pathological changes of podocytes in vitro. Methods: We observed changes in the p130Cas expression in cultured rat GEpCs and mouse podocytes treated with various concentrations of PAN and antioxidants, including probucol, epigallocatechin gallate (EGCG), and vitamin C. The changes in the p130Cas expression level were analyzed using confocal immunofluorescence imaging, Western blotting, and polymerase chain reaction. Results: In the immunofluorescence study, p130Cas showed a diffuse cytoplasmic distribution with accumulation at distinct sites visible as short stripes and colocalized with P-cadherin. The fluorescences of the p130Cas protein were internalized and became granular by PAN administration in a dose-dependent manner, which had been restored by antioxidants, EGCG and vitamin C. PAN also decreased the protein and mRNA expression levels of p130Cas at high doses and in a longer exposed duration, which had been also reversed by antioxidants. Conclusion: These findings suggest that PAN modulates the quantitative and distributional changes of podocyte p130Cas through oxidative stress resulting in podocyte dysfunction.

• The Korean Journal of Physiology and Pharmacology
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• 제14권4호
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• pp.223-228
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• 2010

The collecting duct endothelin (ET) system, which involves ET-1 and its two receptors, may play a role in the regulation of renal sodium in association with the nitric oxide synthase (NOS) system. We determined whether sodium retention is associated with changes in the endothelin and NOS systems at different stages (i.e., a sodium retaining stage and a compensatory stage) of nephrotic syndromes. On day 7 after puromycin aminonucleoside (PAN) injection, urinary sodium excretion was decreased, ascites had developed, and there was a positive sodium balance. ET-1 mRNA expression was increased in the inner medulla of the kidney, whereas protein expression of ET receptor type B ($ET_BR$) was unchanged. The expression of neuronal NOS (nNOS) was decreased in the inner medulla. On day 14, urinary sodium excretion was unchanged compared with controls. The expression of $ET_BR$ increased, while nNOS expression in the inner medulla was comparable to controls. These findings suggest that decreased nNOS plays a role in the development of sodium retention in the nephrotic syndrome. Recovery of nNOS and increased renal $ET_BR$ synthesis may promote sodium excretion in later stages of the nephrotic syndrome (on day 14).

• Childhood Kidney Diseases
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• 제17권2호
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• pp.79-85
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• 2013

목적: 단백뇨 질환의 실험모델인 puromycin aminonucleoside (PAN)에서 관찰할 수 있는 족세포의 병리학적 이상에 있어서 P-cadherin의 변화를 생체 외 족세포 배양실험을 통하여 알아보고자 하였다. 방법: PAN에 의한 족세포의 P-cadherin의 변화를 생체 외 배양실험을 통해 알아보고자 백서 사구체 상피세포(GEpC)를 배양하여 다양한 농도의 PAN을 투여하여 confocal 현미경을 통하여 P-cadherin의 분포를 관찰하였고, Western blotting 과 RT-PCR을 사용하여 P-cadherin 발현의 변화를 관찰하였다. 결과: 외곽세포질에 분포하는 P-cadherin은 단일세포 혹은 응집환경에서 PAN의 농도가 올라갈수록 내부로 응집되는 현상를 볼 수 있었다. Western 분석에서, P-cadherin 단백양은 PAN에 농도-의존적으로, 특히, 고농도인 50 mg/mL에서 24시간과 48시간이 노출 조건에서 각각 21.9% (P< 0.05)와 31.9% (P<0.01)의 의미 있는 감소소견을 보였다. RT-PCR에서도 48시간에서 50 mg/mL PAN을 첨가한 조건에서 23.5%의 의미 있는 감소를 보였다(P<0.05). 결론: PAN은 족세포에서 P-cadherin을 세포막으로부터 내부로의 응집을 유발하고, P-cadherin mRNA의 발현 감소와 단백수준에서 양의 감소를 초래함으로서, 단백뇨의 발생에 기여할 것이라 사료된다.

• Clinical and Experimental Pediatrics
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• 제51권1호
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• pp.54-61
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• 2008

목 적 : 특발성 신증후군의 연구를 위하여 병태생리 및 임상소견과 유사한 실험적 puromycin aminonucleoside(PAN) 신증을 이용하는데 본 연구는 배양한 사구체 상피세포에 대한 PAN의 영향을 통하여 신증후군의 주 원인 병태생리인 단백뇨의 기전을 밝히고자 하였다. 방 법 : 사구체 상피세포를 배양한 후 다양한 농도의 PAN과 항산화제를 투여하여 전자현미경관찰, 반응성 산소종 투과율 변화, confocal microscopy 등을 통하여 족세포성분의 변화를 관찰하였다. 결 과 : 사구체 상피세포의 초고배율소견에서 PAN에 의해 세포간극이 벌어지고 표면의 미세돌기가 단축되는 변화를 볼 수 있었다. 이러한 세포간극의 변화는 세포막부분의 ZO-1에 대한 면역형광검사에서도 확인할 수 있었다. DCF-DA로 측정한 반응성 산소종은 PAN에 의하여 농도에 따라 투여 2시간에 이미 유의한 증가를 보이나, 이러한 변화는 항산화제인 EGCG, probucol, vitamin C에 의해 감소하였다. 또한, 세포단층모델에서 투과율은 PAN에 의하여 농도에 따라 증가하나 항산화제에 의해 증가가 억제되었다. 세포골격구조인 ${\alpha}-actinin$은 사구체 상피세포의 세포질과 바깥 세포막부분으로 actin과 같이 분포하나 고농도의 PAN에 의해 세포질 바깥쪽의 일부분에 집중하는 형상으로 변하였다. 그러나 이러한 변화는 항산화제인 vitamin C의 처치에 의해 예방될 수 있었다. 세극막성분인 ZO-1는 고농도의 PAN에 의해 안쪽으로 이동하고 집중하는 형상으로 변하였으나, vitamin C의 처치에 의해 예방되었다. 이와 함께 ${\alpha}-actinin$과 ZO-1은 PAN에 의해 단백양이 감소하였으나 이는 항산화제에 의해 예방할 수 있었다. 결 론 : PAN은 사구체 상피세포의 반응성 산소종 생성을 증가시키고, 구조성분의 변화를 통하여 형태학적인 변화를 초래하며 이는 투과율의 증가로 나타났다. 이러한 변화들은 항산화제에 의해 어느 정도 억제할 수 있었음으로, PAN은 생체 외 사구체 상피세포에 산화스트레스기전을 통하여 구조적 변화와 이에 따른 단백뇨를 유발시키는 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제13권1호
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• pp.1-7
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• 2009

Sodium retention is a hallmark of nephrotic syndrome. We investigated whether sodium retention is associated with changes of natriuretic peptide system at different stages (i.e., a sodium retaining stage and a compensatory stage) of nephrotic syndrome. At day 7 after PAN(puromycin aminonucleoside) injection, the urinary excretion of sodium was decreased, along with the development of ascites and positive sodium balance. The plasma and urinary ANP(atrial natriuretic peptide) immunoreactivities were increased. ANP mRNA expression was increased in the heart and kidney, whereas that of NPR(natriuretic peptide receptor)-A and NPR-C mRNA was decreased in the kidney. The expression of NEP was decreased in the kidney. At day 14, urinary excretion of sodium did not differ from the control. The plasma ANP level and heart ANP mRNA expression returned to their control values. The expression of ANP mRNA in the kidney was increased in association with increased urinary ANP immunoreactivities. The expression of NPR-A in the kidney became normal, whereas that of NPR-C kept decreased. The expression of NEP(neutral endopeptidase) remained decreased. These findings suggest that the increased renal ANP synthesis in association with decreased metabolism via NEP and NPR-C may play a compensatory role against the development of sodium retention in nephrotic syndrome. The decreased of NPR-A expression in the kidney may contribute to the ANP resistance at day 7. The subsequent recovery of NPR-A expression may play a role in promoting sodium excretion in later stage(at day 14).

• 대한의생명과학회지
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• 제5권1호
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• pp.75-84
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• 1999

선천성 고혈압 흰쥐를 이용하여 puromycin Aminonucleoside (PAN)로 유도된 미세 변화신증에 대한 $\alpha$-tocopherol acetate의 효과를 알아보기 위하여, 정상군, PAN 투여군 (30 mg/kg), 비타민 E 투여군 (200 mg/kg) 그리고 PAN+비타민 E 투여 군으로 나누었다. 각 군은 약물 투여 후 2, 4, 8, 16일째 처치하여 혈청 생화학적 변화, 조직학적 변화, 그리고 미세구조적 변화를 관찰하였다. 실험동물의 체중은 PAN 투여군이 가장 낮은 증가율을 보였고, 비타민 E 투여군이 가장 높은 증가율을 보였다. 혈청 총단백질의 함량은 PAN투여 8일군에서 가장 낮았고, 혈중 요소성 질소와 크레아티닌의 함량은 P투여 8일군에서 가장 높게 나타났다. PAN+비타민 E 투여군에서는 PAN 투여군과 비교하여 혈청 총단백질의 함량이 증가되었고, 혈중 요소성 질소와 크레아티닌의 함량은 감소되었다. 조직학적 관찰 결과, 요세관 공간의 소실과 혈관사이세포의 증식이 PAN 투여 4일군에서 나타나기 시작하여, PAN투여 8일군에서 가장 현저하였으나 비타민 E 투여로 이러한 변화 정도는 감소되었다. PAS 염색 관찰 결과, 염색 정도가 PAN투여 8일군에서 가장 강하게 나타났고, 비타민 E 투여로 염색 정도는 감소되어 나타났다. 미세구조의 변화는 PAN투여 8일군에서 족돌기의 융합과 소실, 모세 혈관 내피세포의 공포화, 그리고 혈관사이세포와 사구체 기저막의 증식이 관찰되었고, 비타민 E투여로 감소되었다. 이러한 결과들로 보아 PAN으로 유도된 사구체 손상은 고혈압에 의해 가중될 수도 있으며, 사구체의 기능이상은 산화적 손상에 의한 것임을 간접적으로 시사하고 있다.