大黄与黄芪对慢性肾衰大鼠的肾保护作用及肠道屏障功能的影响
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篇名: 大黄与黄芪对慢性肾衰大鼠的肾保护作用及肠道屏障功能的影响
TITLE:
摘要: 目的:研究大黄与黄芪对慢性肾衰(CRF)大鼠的肾保护作用及肠道屏障功能的影响,从中医“肠-肾轴”角度分析其药理学作用机制。方法:采用5/6肾切除法复制CRF大鼠模型。将大鼠随机分为假手术组(记为J组,n=6),模型组(记为M组,n=8)和给药组(n=9),即贝那普利组(记为Y组,阳性对照,2 mg/kg),大黄高、中、低剂量组(分别记为DH、DM、DL组,以生药量计分别为3、1.5、0.75 g/kg)和黄芪高、中、低剂量组(分别记为HH、HM、HL组,以生药量计分别为6、3、1.5 g/kg)。各给药组大鼠在成模1周后开始ig给药,每天1次,连续5周;J组和M组大鼠ig等体积蒸馏水。末次给药12 h后,检测大鼠24 h尿蛋白量和血清中肌酐(SCr)、尿素氮(BUN)、尿酸(UA)以及血浆中内毒素水平,计算大鼠肾指数,显微镜下观察大鼠肾组织及小肠黏膜组织肠道绒毛的变化和隐窝深度。结果:与J组比较,M组大鼠24 h尿量、24 h饮水量增加,24 h尿蛋白,血清SCr、BUN、UA,血浆内毒素水平和肾指数升高,差异均有统计学意义(P<0.05或P<0.01);多数肾小球体积增大、硬化,间质有大量炎症细胞浸润;小肠黏膜组织的绒毛长度、绒毛宽度、黏膜厚度及绒毛长度/隐窝深度比均减小(P<0.05或P<0.01),隐窝深度增加(P<0.01)。与M组比较,DM、DL、HM、HL组大鼠24 h尿量减少,HM组大鼠24 h饮水量减少,各给药组大鼠的24 h尿蛋白,血清SCr、BUN水平及肾指数均降低,除HH组外的其余各给药组大鼠的血清UA水平均降低,除HH、HM、HL组外的其余各给药组大鼠的血浆内毒素水平均降低,以上差异均有统计学意义(P<0.05或P<0.01);各给药组大鼠肾组织与肠道绒毛的病理形态均得到不同程度的改善。结论:大黄与黄芪均能有效地降低大鼠代谢毒素水平、提高肾小球滤过功能、增强代谢物的排出;其可能是通过恢复CRF大鼠肠道的功能而达到治疗CRF的目的,且均以中剂量疗效最优。
ABSTRACT: OBJECTIVE: To study the effects of rhei radix and astragali radix on renal protection and intestinal barrier function in rats with chronic renal failure (CRF), and analyze its pharmacological mechanism from the theory of “gut-renal axis” in TCM. METHODS: Rat models of CRF were established by 5/6 nephrectomy. Rats were randomly divided into sham operations group (group J, n=6), model group (group M, n=8), and administration groups (n=9), which included benazepril group (group Y, positive control, 2 mg/kg), rhei radix high-dose, medium-dose, low-dose groups (group DH, DM, DL, calculated by crude drug as 3, 1.5, 0.75 g/kg), and astragali radix high-dose, medium-dose, low-dose groups (group HH, HM, HL, calculated by crude drug as 6, 3, 1.5 g/kg). After 1 week of modeling, rats in each administration group were intragastrically administrated, once a day, for 5 weeks. Rats in group J, M were intragastrically administrated equal volume distilled water. After 12 h of administration, the 24 h urine protein (Upr), serum levels of creatinine (SCr), urea nitrogen (BUN), uric acid (UA) and plasma endotoxin level were detected, and kidney index was calculated. Changes in renal tissue, villi of small intestinal mucosal tissue and crypt depth were observed by microscope. RESULTS: Compared with group J, 24 h urine volume and 24 h water drinking volume of rats in group M were increased, 24 h Upr, serum levels of SCr, BUN, UA, plasma endotoxin level, and kidney index were increased, with statistical significances (P<0.05 or P<0.01). Most glomerular volume were increased and rigid in group M, showing interstitial infiltration in large number of inflammatory cells; villus length, villus width, mucosal thickness and villus length/crypt depth ratio of intestinal mucosa were decreased (P<0.05 or P<0.01), and crypt depth was increased (P<0.01). Compared with group M, 24 h urine volume in group DM, DL, HM, HL was decreased; 24 h water drinking volume in group HM was decreased; 24 h Upr, serum levels of SCr, BUN levels, and kidney index of rats in each administration group were decreased. Except for group HH, serum UA levels in other administration groups was decreased; and except for group HH, HM, HL, plasma endotoxin level in other administration groups was decreased, with statistical significances (P<0.05 or P<0.01). The pathological morphologies of renal tissue, intestinal mucosal tissue and intestinal villi in each administration group were improved to varying degrees. CONCLUSIONS: Both rhei radix and astragali radix can effectively reduce the metabolic toxin levels of rats, improve filtration function of glomerular and enhance the exclusion of metabolic trash, which may be restoring the intestinal function to achieve the goal of treating CRF. And both show optimal effect in medium dose.
期刊: 2017年第28卷第31期
作者: 涂祎珺,李海燕,宫仁豪,钟瑜萍,赖有勤
AUTHORS: TU Yijun,LI Haiyan,GONG Renhao,ZHONG Yuping,LAI Youqin
关键字: 大黄;黄芪;慢性肾衰;肠-肾轴;肠道屏障;大鼠
KEYWORDS: Rhei radix; Astragali radix; Chronic kidney disease; Gut-renal axis; Intestinal barrier; Rats
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