腎毒性PCR芯片可用于研究的84個關(guān)鍵基因的表達(dá)，這些基因可以作為腎毒性的潛在的分子標(biāo)志物。減小腎毒性仍然是新藥上市最大的障礙之一。腎臟是藥物排泄的重要器官，因此它是毒理學(xué)試驗的重要研究對象。在動物模型的毒性反應(yīng)中表達(dá)出現(xiàn)持續(xù)上升或者下降的基因能夠作為預(yù)測不良臨床反應(yīng)的潛在標(biāo)識物。腎臟的排泄過程是從血液經(jīng)過腎小球過濾開始，然后將濾液通過近端小管，亨勒環(huán)路，遠(yuǎn)端腎小管，并最終到達(dá)收集管。藥物引起的腎毒性研究主要集中在近端小管的毒性，大多數(shù)藥物在這個區(qū)域重吸收。該芯片包含已知腎毒性藥物引起的差異表達(dá)的基因。利用實時定量PCR，研究者可以方便并且可信地對與腎毒性反應(yīng)相關(guān)的基因進(jìn)行同時檢測。
Up-Regulated: Apoptosis: ANGPTL4, ANXA5, BTG2, CD24, CD44, CDKN1A, CLU, GADD45A, GSTP1, HMOX1, NQO1, RTN4, SOCS3, TNFRSF12A. Cell Cycle: CCND1, CCNG1, CDKN1A, GADD45A, MCM6. Metal Ion Binding: BMP1, CCS, CP, CTSS, HMOX1, HMOX2, MT1A. Oxidative Stress: CLU, G6PD, GPX2, GPX8, HMOX1, HMOX2, NQO1. Proliferation: ATF3, BTG2, CCND1, CD24, CDKN1A (p21CIP1/WAF1), CLU, CXCL1, CXCL10 (INP10), GLUL, GPNMB, HMOX1, HSP90AA1, TIMP1, UCHL1, VCAM1. Tissue Remodeling: CST3, FN1, HAVCR1 (KIM-1), SPP1 (Osteopontin), TIMP1. Transporters: ABCB1 (MDR1), ABCC2 (MRP2). Xenobiotic Metabolism: CYP2C19, GSTP1. Extracellular Matrix: ANGPTL4, CCL3 (MIP-1A), CD44, CST3, FGB, LGALS3, MGP, TIMP1. Cytoskeleton: CCL3, G6PD, SPRR1A, TMSB10, VIM. Others: A2M, GC, IGFBP1, LCN2 (NGAL), UGT1A1. Down-Regulated: Apoptosis: BMP4, CAT, GHR, IGFBP3, SOD2. Cell Cycle: BMP4, EGF. Metal Ion Binding: BHMT, IDH1, RGN, SCD, SOD2, SOD3. Oxidative Stress: CAT, GATM, IDH1, SOD2, SOD3. Proliferation: BMP4, EGF, IGFBP3, NOX4, ODC1, SOD2. Transporters: SLC22A1, SLC22A5, SLC22A6. Xenobiotic Metabolism: CYP2D6, FMO2, GSTK1. Extracellular Matrix: BMP4, CYR61, SOD3. Others: AASS, ALDH1A1, CALB1, G6PC, GAMT, IPMK, KLK1, NPHS2, OAT. |
