健脾滋肾开郁散结中药对糖尿病肾病大鼠肾损伤的保护作用(1)
[摘要] 目的 探讨健脾滋肾开郁散结中药对链脲佐菌素(STZ)诱导糖尿病肾病(DN)大鼠肾脏病变的影响。 方法 采用高脂高糖饮食加STZ腹腔注射方法建立DN大鼠模型，实验设正常对照组、模型组、健脾滋肾开郁散结中药组(中药组)和盐酸苯那普利加格列喹酮组(西药组)，每组10只。给药后每4周末尾静脉取血，测定各组大鼠的血糖；连续给药12周后，代谢笼收集24 h尿液，检测24 h尿蛋白定量，处死大鼠取血清检测尿素氮(BUN)、肌酐(Scr)、三酰甘油(TG)、胆固醇(TC)、白蛋白(Alb)；另取肾脏组织制石蜡切片行苏木精-伊红(HE)、过碘酸希夫(PAS)染色，观察肾组织的病理改变。 结果 实验结束时模型组大鼠体重较正常对照组明显降低(P < 0.01)，血糖持续升高，至12周末，血糖升至(31.67±5.27)mmol/L，24 h尿蛋白及血清BUN、Scr、TC、TG水平显著升高，与正常对照组比较差异有高度统计学意义(P < 0.01)，其中24 h尿蛋白定量升高至(56.75±10.08)mg/24 h，血清Scr升至(42.63±14.49)mmol/L；光镜下显示肾组织病理变化：肾小球系膜基质增多，部分肾小球系膜细胞增生，毛细血管腔变窄，肾小管上皮细胞水肿，可见空泡变性，肾间质可见炎症细胞增多。与模型组比较，中药组大鼠体重显著升高(P < 0.05)，血糖和24 h尿蛋白定量明显降低(P < 0.05或P < 0.01)，其中血糖从第8周即开始下降，至12周末降至(22.10±3.30)mmol/L；血清BUN、Scr、TC、TG显著降低(P < 0.05或P < 0.01)，Alb显著升高(P < 0.05)，其中血清Scr降至(19.63±4.37)mmol/L。肾组织病理损害亦明显减轻，肾小球系膜基质减少，系膜细胞增生不明显，间质少见炎症细胞浸润。中药组与西药组差异均无统计学意义(P > 0.05)。 结论 健脾滋肾开郁散结中药干预治疗后可降低DN大鼠尿蛋白，改善肾脏功能，在DN的肾损伤过程中具有保护作用。
[关键词] 健脾滋肾开郁散结；中医药；糖尿病肾病；肾组织病理学；大鼠
[中图分类号] R587；R692.3 [文献标识码] A [文章编号] 1673-7210(2015)05(b)-0022-05
Protective effects of Chinese medicine of nourishing spleen and kidney， eliminating stagnation on kidney injury in rats with diabetic nephropathy
ZHANG Mingzhu1 ZHANG Shuping2 LI Wang3 JIN Cunting4 ZHANG Xiaoli5 LI Yingchun2 ZHAO Dongwei2
1.Hebei North University， Hebei Province， Zhangjiakou 075000， China； 2.TCM College， Hebei North University， Hebei Province， Zhangjiakou 075000， China； 3.Academic Affairs Office， Hebei North University， Hebei Province， Zhangjiakou 075000， China； 4.College of Basic Medicine， Heibei North University， Hebei Province， Zhangjiakou 075000， China； 5.Life Sciences Center， Hebei North University， Hebei Province， Zhangjiakou 075000， China
[Abstract] Objective To explore the protective effect of nourishing spleen and kidney， eliminating stagnation on kidney injury in rats with Streptozocin (STZ) induced diabetic nephropathy (DN). Methods High fat and high sugar forage and injection of STZ to abdominal cavity were adopted to establish DN rats model. The animals were assigned randomly to normal control group， model group， therapeutic group treated with decoction of nourishing spleen and kidney， eliminating stagnation (referred to as Chinese herbs group) and therapeutic group treated with Lotensin and Gliguidone (referred to as western medicine group)， with 10 rats per group. Blood was drawn from vein to test blood glucose of rats from each group every 4 weeks； after 12 weeks' successive administration， 24 h urine was collected by metabolism cage to detect 24 h urine protein， and rats were killed to draw blood serum to test blood urea nitrogen (BUN)， serum creatinine (Scr)， triglyceride (TG)， total cholesterol (TC) and albumin (Alb)； kidney tissue was used to make paraffin section to observe renal pathological change by adopting HE and PAS staining. Results As for the rats from model group at the end of the experiment， the weight obviously decreased (P < 0.01) compared with that from normal control group； the blood glucose reached to (31.67±5.27) mmol/L after 12 weeks' continuous increasing； the levels of 24 h urine protein， BUN， Scr， TC and TG significantly increased compared with those from normal control group (P < 0.01)， in which 24 h urine protein increased to (56.75±10.08) mg/24 h and serum creatinine to (42.63±14.49) mmol/L； under optical microscope， the pathological change of renal tissue included glomerular mesangial matrix increase with part of the mesangial cell proliferation， lumen of capillary constriction， hydrops of renal tubular epithelial cell， vacuolar degeneration and more inflammatory cells in renal interstitium. Compared with model group， the weight of Chinese herbs group increased significantly (P < 0.05)； the blood glucose and 24 h urine protein obviously decreased (P < 0.05 or P < 0.01)， in which， the blood glucose started to decrease since the 8th week and dropped to (22.10±3.30) mmol/L at the end of the 12th week； the levels of BUN， Scr， TC and TG significantly decreased (P < 0.05 or P < 0.01)， Alb increased significantly (P < 0.05)， with serum creatinine decreasing to (19.63±4.37) mmol/L； the pathological damage of renal tissue was significantly alleviated， including glomerular mesangial matrix decrease， with slight mesangial cell proliferation and interstitial inflammation. There was no significant difference between two therapeutic groups (P > 0.05). Conclusion The result of our research shows that treatment with nourishing spleen and kidney， eliminating stagnation can reduce DN rats' urine protein， improve its renal function and protect kidney during diabetic-induced kidney injury. (张明柱等)
[关键词] 健脾滋肾开郁散结；中医药；糖尿病肾病；肾组织病理学；大鼠
[中图分类号] R587；R692.3 [文献标识码] A [文章编号] 1673-7210(2015)05(b)-0022-05
Protective effects of Chinese medicine of nourishing spleen and kidney， eliminating stagnation on kidney injury in rats with diabetic nephropathy
ZHANG Mingzhu1 ZHANG Shuping2 LI Wang3 JIN Cunting4 ZHANG Xiaoli5 LI Yingchun2 ZHAO Dongwei2
1.Hebei North University， Hebei Province， Zhangjiakou 075000， China； 2.TCM College， Hebei North University， Hebei Province， Zhangjiakou 075000， China； 3.Academic Affairs Office， Hebei North University， Hebei Province， Zhangjiakou 075000， China； 4.College of Basic Medicine， Heibei North University， Hebei Province， Zhangjiakou 075000， China； 5.Life Sciences Center， Hebei North University， Hebei Province， Zhangjiakou 075000， China
[Abstract] Objective To explore the protective effect of nourishing spleen and kidney， eliminating stagnation on kidney injury in rats with Streptozocin (STZ) induced diabetic nephropathy (DN). Methods High fat and high sugar forage and injection of STZ to abdominal cavity were adopted to establish DN rats model. The animals were assigned randomly to normal control group， model group， therapeutic group treated with decoction of nourishing spleen and kidney， eliminating stagnation (referred to as Chinese herbs group) and therapeutic group treated with Lotensin and Gliguidone (referred to as western medicine group)， with 10 rats per group. Blood was drawn from vein to test blood glucose of rats from each group every 4 weeks； after 12 weeks' successive administration， 24 h urine was collected by metabolism cage to detect 24 h urine protein， and rats were killed to draw blood serum to test blood urea nitrogen (BUN)， serum creatinine (Scr)， triglyceride (TG)， total cholesterol (TC) and albumin (Alb)； kidney tissue was used to make paraffin section to observe renal pathological change by adopting HE and PAS staining. Results As for the rats from model group at the end of the experiment， the weight obviously decreased (P < 0.01) compared with that from normal control group； the blood glucose reached to (31.67±5.27) mmol/L after 12 weeks' continuous increasing； the levels of 24 h urine protein， BUN， Scr， TC and TG significantly increased compared with those from normal control group (P < 0.01)， in which 24 h urine protein increased to (56.75±10.08) mg/24 h and serum creatinine to (42.63±14.49) mmol/L； under optical microscope， the pathological change of renal tissue included glomerular mesangial matrix increase with part of the mesangial cell proliferation， lumen of capillary constriction， hydrops of renal tubular epithelial cell， vacuolar degeneration and more inflammatory cells in renal interstitium. Compared with model group， the weight of Chinese herbs group increased significantly (P < 0.05)； the blood glucose and 24 h urine protein obviously decreased (P < 0.05 or P < 0.01)， in which， the blood glucose started to decrease since the 8th week and dropped to (22.10±3.30) mmol/L at the end of the 12th week； the levels of BUN， Scr， TC and TG significantly decreased (P < 0.05 or P < 0.01)， Alb increased significantly (P < 0.05)， with serum creatinine decreasing to (19.63±4.37) mmol/L； the pathological damage of renal tissue was significantly alleviated， including glomerular mesangial matrix decrease， with slight mesangial cell proliferation and interstitial inflammation. There was no significant difference between two therapeutic groups (P > 0.05). Conclusion The result of our research shows that treatment with nourishing spleen and kidney， eliminating stagnation can reduce DN rats' urine protein， improve its renal function and protect kidney during diabetic-induced kidney injury. (张明柱等)