目的 研究大黄-丹参药对对慢性肾衰竭（CRF）模型大鼠结肠黏液屏障功能的影响。方法 70只雄性Wistar大鼠随机分为假手术组、模型组、尿毒清颗粒组（2.5 g·kg^-1）和大黄-丹参药对高、低剂量组（生药6.0、3.0 g·kg^-1），每组14只。除假手术组外，其余各组大鼠采用5/6肾切除法制备CRF模型。连续ig给药12周后，腹主动脉取血测定血清肌酐（Scr）、尿素氮（BUN）、白细胞介素（IL）-1β、IL-6和肿瘤坏死因子-α（TNF-α）水平；剖取残存肾脏和结肠组织，HE和Masson染色观察大鼠肾组织形态学和纤维化改变；阿利新蓝-过碘酸-雪夫（AB-PAS）染色观察结肠黏液层厚度和杯状细胞数量变化；免疫组化观察大鼠结肠组织黏蛋白2（Muc2）阳性表达；采用实时荧光定量（qRT-PCR）法和蛋白免疫印记（Westernblotting）法检测大鼠结肠组织Muc2的mRNA和蛋白表达情况。结果 与假手术组相比，模型组大鼠血清Scr、BUN、IL-1β、IL-6和TNF-α水平明显升高（P＜0.01）；肾组织中肾小球硬化、肾小管扩张，肾间质可见炎性细胞浸润和纤维化，纤维化评分显著增加（P＜0.01）；结肠黏液层变薄，杯状细胞减少；结肠组织Muc2阳性表达降低，结肠组织Muc2的mRNA和蛋白表达水平均降低（P＜0.01）。与模型组比较，大黄-丹参药对高、低剂量组能显著降低模型大鼠血清Scr、BUN、IL-1β、IL-6和TNF-α水平（P＜0.01）；肾组织形态明显改善，肾纤维化评分显著降低（P＜0.01）；结肠黏液层厚度增加，杯状细胞增多；结肠组织Muc2阳性表达升高，结肠组织Muc2的mRNA和蛋白表达水平明显升高（P＜0.01）。结论 大黄-丹参药对能够有效保护CRF大鼠的残存肾功能，延缓CRF进展；其机制可能与恢复CRF大鼠结肠黏液屏障功能，改善机体炎症状态有关。

Objective To study the effects of Rheum palmatum-Salvia miltiorrhiza drug pairs (RS) on colonic mucus barrier function in rats with chronic renal failure (CRF). Methods Seventy male Wistar rats were randomly divided into sham-operation group, model group, Niaoduqing Granule (2.5 g·kg^?1) group, RS high and low dose groups (6, 3 g crude drug·kg^?1), with 14 rats in each group. Except the sham-operation group, the CRF models were replicated by 5/6 nephrectomy. After continuous ig administration for 12 weeks, the levels of serum creatinine (Scr), urea nitrogen (BUN), interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were measured with blood collected from abdominal aorta. The remaining kidney and colon tissue were dissected, the changes of renal histology and fibrosis were observed by HE and Masson staining. The changes of mucous layer thickness and goblet cell number in colon were observed by AB-PAS staining. The positive expression of Muc2 protein in colon tissues of rats was observed by immunohistochemistry. The expressions of Muc2 mRNA and protein in colon tissues was detected by real-time fluorescent quantitative PCR (qRT-PCR) and Western blotting. Results Compared with sham-operation group, the levels of serum Scr, BUN, IL- 1β, IL-6 and TNF- α of rats in model group were significantly increased (P < 0.01), glomerular sclerosis, renal tubule dilation, inflammatory cell infiltration and fibrosis were observed in renal interstitium, and the fibrosis score was significantly increased (P <0.01), the mucus layer of colon was thinner and the number of goblet cells were reduced, the positive expression of Muc2 in colon tissue were decreased, and the expression levels of Muc2 mRNA and protein in colon tissues were decreased (P < 0.01). Compared with the model group, RS could significantly reduce the levels of serum Scr, BUN, IL-1β, IL-6 and TNF-α in high and low dose groups (P < 0.01), the renal tissue morphology was significantly improved, and the renal fibrosis score was significantly decreased (P < 0.01), the thickness of colon mucus layer increased and the number of goblet cells increased, the positive expression of Muc2 in colon tissue were increased, the expression level of Muc2 mRNA and protein in colon tissues were significantly increased (P < 0.01). Conclusion RS could effectively protect the residual renal function of CRF rats and delay the progression of CRF. The mechanism might be related to the restoration of colonic mucus barrier function and improvement of inflammatory state of CRF rats.

R285.5

天津市卫生健康委员会天津市中医药管理局中医中西医结合科研课题（2021163）