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1、糖化终末产物糖化终末产物肾小球高肾小球高滤过肥厚滤过肥厚氧化应激氧化应激PKC多元醇通路多元醇通路活性活性TGF-Ang-GH/IGF-NO白介素高血压、高高血压、高血脂、吸烟血脂、吸烟遗遗 传传糖尿病肾病的发病机制高血糖高血糖 糖尿病肾病糖尿病肾病Adapted from Breyer JA et al. Am J Kid Dis 1992; 20(6): 535.时间时间 ( (年年) )05 520203030糖尿病开始糖尿病开始 蛋白尿开始蛋白尿开始终末期肾病终末期肾病结构改变结构改变( (肾小球基底膜增多且系膜扩展肾小球基底膜增多且系膜扩展) )高血压高血压明显肾病明显肾病(Scr,
2、(Scr,升高升高GFRGFR降低降低)初期肾病初期肾病( (高滤过高滤过, ,微白蛋白尿微白蛋白尿, ,血压升高血压升高)临床前的肾病临床前的肾病美国肾脏基金会肾脏病预后质量倡议(NKFKDOQI)指南标准光学显微镜检查光学显微镜检查糖尿病肾病的基本病理变化糖尿病肾病的基本病理变化呈现两种病理类型呈现两种病理类型Sl i de 3 N orm al gl om erul us: Hem atoxyl i n andeosi n st ai n of a norm al gl om erul us sect i onedt hrough the vascul ar pol e. N ot e
3、the w i de-opencapi l l ary l um i na and the l arge percent age of thecross-secti onal area of the gl om erul us devot ed t ot he capi l l ary ci rcul at i on. The m esangi al cel l ul ari t yand m at ri x are norm al .Sl i de 1 N orm al gl om erul us: Schem at i zeddraw i ng of a norm al gl om eru
4、l us show i ng epi t hel i alcel l s i n green, endot hel i al cel l s i n yel l ow andm esangi al cel l s i n red. N ot e t hat t he gl om erul arbasem ent m em branes (i n bl ack) do notcom pl et el y surround capi l l ary l oops, and t hatendot hel i al cel l s are i n di rect cont act w i t hm e
5、sangi al m at ri x (bl ue) at t he m esangi al pol esof capi l l ari es.Burton D RoseBurton D Rose，MD 2000MD 2000Sl i de 165 Di abet i c nephropat hy: Thi sschem at i zed draw i ng show s t he m arkedl yt hi ckened l am i na densa of t he GBM andi ncreased m esangi al m at ri x m at eri alw hi ch ar
6、e t he si ne qua non of di abet i c renaldi sease. The subsequent sl i des (166-202)dem onst rat e t he spect rum of di abet i c renaldi sease (st art i ng w i t h a revi ew of norm algl om erul ar hi st ol ogy), and i l l ust rat e di st i ngui shi ngpoi nt s bet w een ot her t ypes of gl om erul o
7、pat hi esw hi ch m ay m i m i c di abet i c nephropat hy.糖尿病肾病：肾小球基底膜增厚伴系膜基质扩张Sl i de 167 M oderat e di f f use di abet i cgl om erul oscl erosi s i n an i nsul i n-dependentdi abet i c (I DDM ) pat i ent w i t h 16 years durat i on.N ot e t he w i deni ng of t he gl om erul ar m esangi um ,t he res
8、t ri ct i on of t he gl om erul ar capi l l aryci rcul at i on, t he t hi ckeni ng of t he gl om erul arbasem ent m em brane com pared t o sl i de 1, and t hehyal i nosi s of t he art eri ol ar w al l at t he vascul arpol e (PAS).弥漫性轻度糖尿病肾小球硬化：系膜区基质扩张，GBM增厚，毛细血管腔受压，血管极小动脉壁增厚Sl i de 168 M arked di f
9、f use di abet i cgl om erul oscl erosi s. There i s ext rem e expansi onof t he m esangi um w i t h bot h m at ri x and cel l ul arm at eri al . The capi l l ary l um enal ci rcul at i on i sm arkedl y const ri ct ed (PAS). W hereas t hepat i ent i n sl i de 2 had norm al renal f unct i on, t hi spa
10、t i ent had overt nephropat hy w i t h prot ei nuri a,hypert ensi on, and a 50% reduct i on i n GFR.弥漫、严重糖尿病肾小球硬化：系膜区基质及细胞显著增加，毛细血管腔严重受压；该患者肾小球滤过率下降50%，伴显著蛋白尿、严重高血压光学显微镜检查光学显微镜检查糖尿病肾病的病理变化糖尿病肾病的病理变化S lid e 171 N o d u lar d iab etic g lo m eru lo sclero sis(K im m elstiel-W ilso n lesio n s) in a p
11、atien t w itho vert d iab etic n ep h ro p ath y an d p ro tein u ria,h yp erten sio n , an d red u ced G FR . N o te th ep alisad in g o f m esan g ial n u clei aro u n d th ep erip h ery o f th e n o d u le an d th e fib rillar n atu reo f th e n o d u lar m atrix m aterial. N o te also th erestri
12、ctio n o f g lo m eru lar cap illary lu m en al sp ace(P A S ).结节性肾小球硬化（K-W结节）：伴蛋白尿、高血压及肾小球滤过率下降糖尿病肾病的糖尿病肾病的其他其他病理变化病理变化Sl i de 178 A capsul ar drop consi st i ng of hyal i nePAS posi t i ve m at eri al deposi t ed on t he pari et alsurf ace of Bow m an s m em brane (9 o cl ock).帽状滴：透明PAS阳性物质沉积于肾小球囊
13、之内侧壁Sl i de 179 Form at i on of a capsul ar drop byadhesi on of gl om erul ar capi l l ary l oops cont ai ni ngsubendot hel i al hyal i ne (t he so-cal l ed “ exudat i vel esi on” ) t o Bow m an s capsul e (9 o cl ock and11 o cl ock). I t i s l i kel y t hat t he gl om erul ar capi l l aryl oops ret
14、 ract , deposi t i ng t he hyal i ne m at eri al al ongt he Bow m an s capsul ar w al l .帽状滴之形成：肾小球毛细血管袢渗出性物质（内皮细胞下透明样物质）附着与肾小球囊之内侧壁，然后肾小球收缩。小动脉透明样变性（右图）Sl i de 174 Earl y gl om erul ar art eri ol ar hyal i nosi si n an af f erent art eri ol e. N ot e t he sm oot h, w axy,hom ogenous PAS posi t i ve
15、 m at eri al i n t hesubendot hel i al space. Thi s I DDM pat i ent hadnorm al renal f unct i on.入球小动脉透明样变性早期改变：内皮细胞下非细胞均质成份沉积，肾功能尚正常Sl i de 176 Art eri ol ar hyal i nosi s i n bot h af f erent(l ow er l ef t si de) and ef f erent (l ow er ri ght si de)gl om erul ar art eri ol es (PAS). N ot e t he
16、di f f use andnodul ar di abet i c gl om erul oscl erosi s i n t hi s I DDMpat i ent w i t h earl y overt nephropat hy.入球小动脉与出球小动脉壁透明样变，弥漫性糖尿病结节性肾小球硬化：型糖尿病引起的临床糖尿病肾病之早期Sl i de 175 Advanced art eri ol ar hyal i nosi s w i t hvi rt ual com pl et e repl acem ent of t he vessel w al l byhyal i ne w axy m at eri al (PAS).蜡样物质填充于小动脉壁，引起血管腔几乎完全闭塞Sl i de 200 Thi s and t he subsequent t w o sl i desi l l ust rat e t he at ypi cal l esi ons com m onl y seen i nm i croal bum i nuri c N I DDM pat i ent s. S
