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加味六味地黄汤对CKD-MBD模型大鼠肾/骨组织损伤的影响
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篇名: 加味六味地黄汤对CKD-MBD模型大鼠肾/骨组织损伤的影响
TITLE: Effects of Modified Liuwei Dihuang Decoction on Kidney/Bone Injury of CKD-MBD Model Rats
摘要: 目的:研究加味六味地黄汤对慢性肾脏病矿物质和骨异常(CKD-MBD)模型大鼠肾/骨组织损伤的影响。方法:将雄性SD大鼠随机分为正常组(n=10)、单纯高磷组(n=30)、模型组(n=30)、骨化三醇组(阳性对照,0.09μg/kg,n=30)和加味六味地黄汤组(以生药总量计10g/kg,n=30)。采用高磷联合腺嘌呤饲料饲养6周的方法建立CKD-MBD模型。造模后,正常组和模型组大鼠继续以普通饲料/高磷饲料饲养并灌胃蒸馏水;各药物组大鼠改为普通饲料饲养并灌胃相应药液(溶剂均为水);按0.1mL/kg每天按时灌胃1次,连续6周。正常组大鼠末次给药后取血、处死,其余各组大鼠分别于给药2、4、6周时随机取10只取血、处死。检测各组大鼠血清中尿素氮(BUN)、血肌酐(Scr)、钙、磷、全段甲状旁腺激素(iPTH)、成纤维细胞生长因子23(FGF-23)、核因子κB受体活化因子配体(RANKL)和骨钙素含量,测定股骨头的骨密度,观察肾组织和骨组织的形态学变化并计算肾小管损伤百分比和肾间质纤维化分值。结果:与正常组比较,单纯高磷组大鼠各时间点上述指标均无明显变化(P>0.05),肾/骨组织亦无异常改变。与单纯高磷组相同时间点比较,模型组大鼠各时间点血清中BUN、Scr、磷、iPTH、FGF-23、RANKL、骨钙素含量和肾小管损伤百分比、肾间质纤维化分值均显著升高,血清中钙含量和股骨头的骨密度均显著降低(P<0.05或P<0.01),肾组织呈弥散性纤维化,骨小梁宽度增加、成骨细胞减少。与模型组相同时间点比较,加味六味地黄汤组和骨化三醇组大鼠各时间点血清中BUN(加味六味地黄汤组给药2周除外)、Scr、血磷、iPTH、FGF-23、RANKL、骨钙素含量和肾小管损伤百分比、肾间质纤维化分值均显著降低,血清中钙含量和骨密度(给药2周除外)均显著升高(P<0.05或P<0.01),肾/骨组织病理变化明显改善;而加味六味地黄汤组和骨化三醇组上述各指标差异均无统计学意义(P>0.05)。结论:加味六味地黄汤可改善CKD-MBD模型大鼠肾/骨组织损伤,提高其骨密度并调节钙磷代谢紊乱。
ABSTRACT: OBJECTIVE:To study the effects of Modified liuwei dihuang decoction on kidney/bone injury of chronic kidney disease-mineral and bone disorder(CKD-MBD)model rats. METHODS :The male SD rats were randomly divided into normal group(n=10),high phosphorus group (n=30),model group (n=30),calcitriol group (positive control ,0.09 μg/kg,n=30), Modified liuwei dihuang decoction group (10 g/kg by crude drug ,n=30). CKD-MBD model was established by high phosphorus and adenine diet for 6 weeks. After modeling ,normal group and model group were given normal diet/high phosphorus diet and intragastric administration of water. Administration groups were fed with normal diet and given corresponding solution intragastrically(water as solvent ),0.1 mL/kg,once a day ,for consecutive 6 weeks. Blood sample of rats in the normal group were collected ,and they were sacrificed after the last administration. Blood sample of 10 rats in each other group were collected , and they were sacrificed at 2,4 and 6 weeks after administration. The contents of blood urea nitrogen (BUN),serum creatinine (Scr),calcium,phosphorus,iPTH,FGF-23,RANKL and osteocalcin in serum were detected in each group. The bone mineral density(BMD)of femoral was measured ,the morphological changes of renal tissue and bone tissue were observed ,and the percentage of renal tubular injury and the score of renal interstitial fibrosis were calculated. RESULTS :Compared with normal group,above indexes in high phosphorus group had no significant change at different time points (P>0.05). There was no abnormal change in renal/bone tissue. Compared with high phosphorus group at the same time point ,the contents of BUN ,Scr, phosphorus,iPTH,FGF-23,RANKL and osteocalcin in serum ,the percentage of renal tubular injury and the score of renal interstitial fibrosis in the model group were significantly increased ,while the contents of calcium in serum and the BMD of femoral were significantly decreased (P<0.05 or P<0.01). The renal tissue showed diffuse fibrosis. The width of trabecular bone was increased and the number of osteoblasts was decreased. Compared with the model group at the same time point ,the contents of BUN(except for Modified liuwei dihuang decoction group after 2 weeks of administration ),Scr,serum phosphorus ,iPTH, FGF-23,RANKL and osteocalcin ,the percentage of renal tubular injury and the score of renal interstitial fibrosis in Modified liuwei dihuang decoction group and calcitriol group were decreased significantly at each time point ;serum calcium content and BMD(except for 2 weeks of administration )were significantly increased (P<0.05 or P<0.01),and the pathological changes of renal/bone tissue were significantly improved ;there was no statistical significance in above indexes between Modified liuwei dihuang decoction group and calcitriol group (P>0.05). CONCLUSIONS :Modified liuwei dihuang decoction can improve kidney/ bone injury of CKD-MBD model rats ,and improve BMD and regulate disorder of calcium and phosphorus metabolism.
期刊: 2021年第32卷第06期
编辑: 郭华慧,梁群卿,李贺生,杨义龙,黄家晟,陈鹏辉,兰聪颖,黄仁发
AUTHORS: GUO Huahui,LIANG Qunqing, LI Hesheng,YANG Yilong,HUANG Jiasheng,CHEN Penghui,LAN Congying,HUANG Renfa
关键字: 加味六味地黄汤;慢性肾病矿物质和骨代谢异常;肾组织;骨组织;损伤;大鼠
KEYWORDS: Modified liuwei dihuang decoction ;Chronic kidney disease-mineral and bone disorder;Renal tissue ;Bone tissue ;
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