To examine the effect of multi-glycoside of Tripterygium wilfordii Hook. f. （GTW） on proteinuria and acute glomerular immune lesion in experimental mesangial proliferative glomerulonephritis （MsPGN） induced by ant...To examine the effect of multi-glycoside of Tripterygium wilfordii Hook. f. （GTW） on proteinuria and acute glomerular immune lesion in experimental mesangial proliferative glomerulonephritis （MsPGN） induced by anti-Thyl. 1 monoelonal antibody （mAb） 1-22-3. The reversible model of MsPGN with anti-Thyl. 1 mAb 1-22-3 was established. After 7 days of oral treatment with GTW （ 100 mg/kg per day） and vehicle （distilled water, 5 ml/kg per day）, its effects on proteinuria, renal functions, mesangial morphological change, glomerular macrophage accumulation, and mRNA expressions of cytokines （PDGF-BB and MCP-1 ） were evaluated by light microscope （LM）, immunofluorescence （IF）, and reverse transcription polymerase chain reaction （RT-PCR）. It was found that GTW ameliorated proteinuria （on day 3 and day 7）, mesangial proliferation （total cell number, matrix expansion, a-smooth muscle actin expression, and collagen type Ⅰ expression） and macrophage accumulation （ED3^＋ ） in experimental MsPGN. In addition, GTW significantly suppressed the increased mRNA expressions for MCP-1 （67.6% to eontrol group, P 〈 0.01） together with the tendency to reduce the expression of PDGF （24.44% to control group） on day 7. It is concluded that GTW can not only decrease proteinuria, but also ameliorate acute mesangial alterations and glomerular activated macrophage accumulation probably by reduction of cytokines. These data indicate that GTW is an effective agent for early MsPGN.展开更多
Adenine is commonly used to establish the animal models for chronic kidney injury and its renal interstitial fibrosis. As an endogenous substance, adenine-induced kidney damage has not yet been fully studied and eluci...Adenine is commonly used to establish the animal models for chronic kidney injury and its renal interstitial fibrosis. As an endogenous substance, adenine-induced kidney damage has not yet been fully studied and elucidated, except for inflammatory reaction. Here we analyzed the proteomics of kidney of rats after adenine overloading using LS-MS/MS assay, and observed the role of anemoside B4(B4). The results showed that adenine could down-regulate 285 proteins and up-regulate 164 proteins in rat kidney tissue compared with the normal group. Down-regulated proteins mainly affected related pathways, such as energy metabolism, while up-regulated proteins affected inflammatory response pathways and metabolic pathways. B4 could significantly reverse the down-regulation of about 40 proteins, which were involved in mitochondria, redox processes, extracellular exosomes, acetylation and other signaling pathways. Simultaneously, B4 could inhibit the up-regulation of five proteins caused by adenine, which were involved in cell cycle, oocyte meiosis, PI3 K-Akt and other signaling pathways. Further experimental results of mRNA expression using real-time PCR assay supported the proteomic analysis. Therefore, we proposed that the damage of rat kidney caused by adenine was more complicated, not only with an inflammatory reaction, but also with extensive effects to various metabolic processes in the body. This work provided a valuable clue for comprehensive understanding of adenine-induced renal damage.展开更多
文摘To examine the effect of multi-glycoside of Tripterygium wilfordii Hook. f. （GTW） on proteinuria and acute glomerular immune lesion in experimental mesangial proliferative glomerulonephritis （MsPGN） induced by anti-Thyl. 1 monoelonal antibody （mAb） 1-22-3. The reversible model of MsPGN with anti-Thyl. 1 mAb 1-22-3 was established. After 7 days of oral treatment with GTW （ 100 mg/kg per day） and vehicle （distilled water, 5 ml/kg per day）, its effects on proteinuria, renal functions, mesangial morphological change, glomerular macrophage accumulation, and mRNA expressions of cytokines （PDGF-BB and MCP-1 ） were evaluated by light microscope （LM）, immunofluorescence （IF）, and reverse transcription polymerase chain reaction （RT-PCR）. It was found that GTW ameliorated proteinuria （on day 3 and day 7）, mesangial proliferation （total cell number, matrix expansion, a-smooth muscle actin expression, and collagen type Ⅰ expression） and macrophage accumulation （ED3^＋ ） in experimental MsPGN. In addition, GTW significantly suppressed the increased mRNA expressions for MCP-1 （67.6% to eontrol group, P 〈 0.01） together with the tendency to reduce the expression of PDGF （24.44% to control group） on day 7. It is concluded that GTW can not only decrease proteinuria, but also ameliorate acute mesangial alterations and glomerular activated macrophage accumulation probably by reduction of cytokines. These data indicate that GTW is an effective agent for early MsPGN.
基金National Innovative Drugs 13th Five-Year Major Special Project of China(Grant No.2018ZX09301030-002)
文摘Adenine is commonly used to establish the animal models for chronic kidney injury and its renal interstitial fibrosis. As an endogenous substance, adenine-induced kidney damage has not yet been fully studied and elucidated, except for inflammatory reaction. Here we analyzed the proteomics of kidney of rats after adenine overloading using LS-MS/MS assay, and observed the role of anemoside B4(B4). The results showed that adenine could down-regulate 285 proteins and up-regulate 164 proteins in rat kidney tissue compared with the normal group. Down-regulated proteins mainly affected related pathways, such as energy metabolism, while up-regulated proteins affected inflammatory response pathways and metabolic pathways. B4 could significantly reverse the down-regulation of about 40 proteins, which were involved in mitochondria, redox processes, extracellular exosomes, acetylation and other signaling pathways. Simultaneously, B4 could inhibit the up-regulation of five proteins caused by adenine, which were involved in cell cycle, oocyte meiosis, PI3 K-Akt and other signaling pathways. Further experimental results of mRNA expression using real-time PCR assay supported the proteomic analysis. Therefore, we proposed that the damage of rat kidney caused by adenine was more complicated, not only with an inflammatory reaction, but also with extensive effects to various metabolic processes in the body. This work provided a valuable clue for comprehensive understanding of adenine-induced renal damage.
