目的 研究大黃-丹參藥對(duì)對(duì)慢性腎衰竭（CRF）模型大鼠結(jié)腸黏液屏障功能的影響。方法 70只雄性Wistar大鼠隨機(jī)分為假手術(shù)組、模型組、尿毒清顆粒組（2.5 g·kg^-1）和大黃-丹參藥對(duì)高、低劑量組（生藥6.0、3.0 g·kg^-1），每組14只。除假手術(shù)組外，其余各組大鼠采用5/6腎切除法制備CRF模型。連續(xù)ig給藥12周后，腹主動(dòng)脈取血測定血清肌酐（Scr）、尿素氮（BUN）、白細(xì)胞介素（IL）-1β、IL-6和腫瘤壞死因子-α（TNF-α）水平；剖取殘存腎臟和結(jié)腸組織，HE和Masson染色觀察大鼠腎組織形態(tài)學(xué)和纖維化改變；阿利新藍(lán)-過碘酸-雪夫（AB-PAS）染色觀察結(jié)腸黏液層厚度和杯狀細(xì)胞數(shù)量變化；免疫組化觀察大鼠結(jié)腸組織黏蛋白2（Muc2）陽性表達(dá)；采用實(shí)時(shí)熒光定量（qRT-PCR）法和蛋白免疫印記（Westernblotting）法檢測大鼠結(jié)腸組織Muc2的mRNA和蛋白表達(dá)情況。結(jié)果 與假手術(shù)組相比，模型組大鼠血清Scr、BUN、IL-1β、IL-6和TNF-α水平明顯升高（P＜0.01）；腎組織中腎小球硬化、腎小管擴(kuò)張，腎間質(zhì)可見炎性細(xì)胞浸潤和纖維化，纖維化評(píng)分顯著增加（P＜0.01）；結(jié)腸黏液層變薄，杯狀細(xì)胞減少；結(jié)腸組織Muc2陽性表達(dá)降低，結(jié)腸組織Muc2的mRNA和蛋白表達(dá)水平均降低（P＜0.01）。與模型組比較，大黃-丹參藥對(duì)高、低劑量組能顯著降低模型大鼠血清Scr、BUN、IL-1β、IL-6和TNF-α水平（P＜0.01）；腎組織形態(tài)明顯改善，腎纖維化評(píng)分顯著降低（P＜0.01）；結(jié)腸黏液層厚度增加，杯狀細(xì)胞增多；結(jié)腸組織Muc2陽性表達(dá)升高，結(jié)腸組織Muc2的mRNA和蛋白表達(dá)水平明顯升高（P＜0.01）。結(jié)論 大黃-丹參藥對(duì)能夠有效保護(hù)CRF大鼠的殘存腎功能，延緩CRF進(jìn)展；其機(jī)制可能與恢復(fù)CRF大鼠結(jié)腸黏液屏障功能，改善機(jī)體炎癥狀態(tài)有關(guān)。

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

天津市衛(wèi)生健康委員會(huì)天津市中醫(yī)藥管理局中醫(yī)中西醫(yī)結(jié)合科研課題（2021163）