Renal Toxicology Study Of CVB-D

CVB-D is a monomer alkaloid which extracted from Buxus microphylla.CVB-D is a new drug that our contry developed to cure cerebrovascular disease,its trade name is HUANGYANGNING.Much study was concentrated on the pharmacology and the pharmacodynamic action,while its toxicology study report was very little.Previous research informations demonstrated that CVB-D used by the way of large dose and long-term can damage some organs such as liver,heart and kidney.Two-months exeriment that ip CVB-D in rats indicated that some rats in large group appeared abnormal phenomenons such as reaction dullness,low spirits,breathlessness and slow weight gain.CVB-D can heighten some indexes content such as BUN,β₂-MG in rats blood serum,while decrease the content of THP.CVB-D can heighten some indexes content such as NAG,β-GAL,mAlb,RBP,TRF,β₂-MG,IgG and Cl^- in rats urine.TRF,mAlb,IgG etc.belong to ecule protein,which cannot be filtered out from acinus renis.These indexes can be filtered out from acinus renis only when the function of glomerular filtration was damaged.While another micromolecule protein,such asβ₂-MG,RBP etc.can be reabsorbed by proximal nephric tubule after filtering out from acinus renis.The increase of these micromolecule protein and urease,for example,the NAG andβ-GAL,can reflect the damage of proximal nephric tubule.The rat histopathologic slides were found that CVB-D can result the phenomenons of renal interstitium inflammation,the damage of acinus renis and nephric tubule.The cell experiment indicated that large dose CVB-D can restrain RTECs proliferation,its IC₅₀ is 111.76μmol/L.CVB-D can result the phenomenons of RTECs shrinkage and vacuolization even breakage.CVB-D can increase the content of LDH in RTECs culture fluid. By further study,we found that CVB-D can promote RTECs apoptosis and restrain the vigor of Na⁺,K⁺-ATPase in RTECs.This experiment reveal that CVB-D can destroy the filter membrane barrier and electrostatic barrier of acinus renis,which result the leakage of ecule protein in urine.CVB-D can damage proximate nephric tubule,and result disce of the proximate tubular reabsorption, which can prevent nephric tubule to reabsorb some low molecular weight protein,for exemple, theβ₂-MG,RBP etc.which accordingly increase the content of these low molecular weight protein in urine.The damage mechanisms of RTECs by CVB-D is possiblely through the way of damaging RTECs directly,promoting RTECs apoptosis and restraining the vigor of Na⁺,K⁺-ATPase in RTECs.