OBJECTIVETo examine suppressive effects of multi-glycoside of Tripterygium wilfordii Hook. f. (GTW)on mesangial injury induced by two-injecti on of anti-Thy1. 1 monoclonal antibody(mAb) 1-22-3 in vitro.

METHODWe established the irreversible model of glomerulosclerosis with anti-Thy1. 1 mAb 1-22-3. After 42 days of oral treatment with GTW (50 mg x kg(-1) BW)and vehicle (distilled water), to observe effects of GTW on proteinuria, renal function, mesangial morphological change, and mRNA expressions of collagen type I and TGF-beta by light microscope (LM), immunofluorescence (IF), and Reverse Transcription Polymerase Chain Reaction (RT-PCR).

RESULTGTW ameliorated proteinuria (from day24 to day 42) and mesangial proliferation [total cell number, GTW group 65.67+/-3.43 vs. control group 87.02+/-2.41, P < 0.05; matrix expansion, GTW group 1.20+/-0.06 vs. control group 2.77+/-0.23, P < 0.05; alpha-smooth muscle actin(alpha-SMA) expression, GTW group 1.75+/-0.33 vs. control group 2.62+/-0.15, P < 0.05; collagen type I expression, GTW group 1.68+/-0.31 vs. control group 2.06+/-0.24, P < 0.05], moreover, significantly reduced the glomerular expression of mRNA for collagen type 1(53.5% to the control group, P < 0.05)and TGF-beta(14.7% to the control group, P < 0.05)on day 42day.

CONCLUSIONGTW can not only decrease proteinuria, but also ameliorate mesangial alterations probably by the reduction of cytokines. GTW may be a promising agent for the prevention of progressive and irreversible glomerulosclerosis.

Actinin ; metabolism ; Animals ; Collagen Type I ; biosynthesis ; genetics ; Female ; Glomerular Mesangium ; metabolism ; pathology ; Glomerulonephritis, Membranoproliferative ; metabolism ; pathology ; Glycosides ; isolation & purification ; pharmacology ; Plants, Medicinal ; chemistry ; Proteinuria ; drug therapy ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Rats, Wistar ; Transforming Growth Factor beta ; biosynthesis ; genetics ; Tripterygium ; chemistry

The anti-Thy1.1 glomerulonephritis (GN) model induced by anti-Thy1.1 monoclonal antibody (mAb) is a widely used animal model for human mesangial proliferative glomerulonephritis (MsPGN), which is characterized by significant proteinuria and acute or progressive mesangial injury following the complement-mediated mesangiolysis and glomerular inflammatory cell infiltration. In this review, it has been discussed that the pathogenesis of reversible anti-Thy1.1 GN or irreversible anti-Thy1.1 GN induced by mAb 1-22-3 injection, the mechanisms governing inflammatory cells infiltration and several injurious cytokines in glomeruli, and some of the processes involved in the resolution of mesangial lesion such as mesangial cell proliferation and matrix expansion. Using these models, it has been reported to examine the effects of Chinese materia medica, including multi-glycoside of Tripterygium wilfordii Hook. f. (GTW) and Sairei-to on mesangial damage and proteinuria, and then to clarify the mechanism of these herbs at molecular level by examining the effects on various injurious factors.
Animals ; Antibodies, Monoclonal ; immunology ; Cytokines ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Glomerulonephritis ; immunology ; metabolism ; prevention & control ; Glycosides ; isolation & purification ; pharmacology ; Humans ; Thy-1 Antigens ; immunology ; Tripterygium ; chemistry