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NC group received 1 cm transverse incision performed at the body surface anatomical position of the right kidney and sutured，
and intraperitoneal injection of citric acid buffer when the wound healed one week later. Those in model group were treated with
right nephrectomy，and received a single intraperitoneal injection of STZ solution（55 mg/kg） with the same volume as the
citric acid buffer for the NC group one week later to establish the DKD model. Then rats in the model group were randomly divided
into DKD subgroup（n=10） and QRXZF subgroup（n=10） when the modeling was successfully achieved. After this，rats in
NC group and DKD subgroup received intragastric administration of the same amount（1 ml/100 g） of 0.9% sodium chloride
solution once a day，and those in QRXZF subgroup received intragastric administration of QRXZF at a dose of 7.92 g·kg -1
-1
·d . During the intervention，weight was measured every week. After 16 weeks of intervention，a 24-hour urine，serum and
kidney tissue specimens were collected，kidney weight was measured，and the kidney weight index was calculated. Enzyme-
linked immunosorbent assay was used to detect the microalbumin in 24-hour urine（24 hUpro）. The automatic biochemical
analyzer was used to analyze serum creatinine（Scr），blood urea nitrogen（BUN） and serum albumin（ALB）. Hematoxylin-
eosin staining，Periodic Acid-Schiff staining and Masson's trichrome staining were performed to observe the damage degree of
kidney tissue. Immunohistochemical method was used to detect the expression level of Caspase-3 and p16 in kidney tissue. The
apoptosis of renal tubular cells was detected by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling.
Results Compared with rats in the NC group，those in DKD and QRXZF subgroups had lower weight and higher kidney weight
index（P<0.01）. Rats in QRXZF subgroup had higher weight and lower kidney weight index than those in DKD subgroup
（P<0.01）. In comparison to rats in the NC group，rats in DKD subgroup had higher levels of 24 hUpro，Scr and BUN lower
level of ALB（P<0.01），and those in QRXZF subgroup had higher levels of 24 hUpro and BUN，and lower level of ALB （P<0.01）.
Rats in QRXZF subgroup had higher levels of 24 hUpro，Scr and BUN，and lower level of ALB than did those in DKD subgroup
（P<0.01）. Compared with rats in the NC group，obvious pathological injury，glomerular hypertrophy and interstitial tubular
fibrosis were observed in kidney tissues in rats of both DKD and QRXZF subgroups，but the degree of pathological changes was
much lighter in QRXZF subgroup. Immunohistochemistry analysis showed that the expression levels of P16 and Caspase-3 in renal
tissue in DKD or QRXZF subgroup were higher than those in NC group（P<0.01）. The expression levels of P16 and Caspase-3
in renal tissue in QRXZF subgroup were lower than those in DKD subgroup（P<0.01）. The rate of renal tubular cell apoptosis
in DKD or QRXZF subgroup was higher than that in NC group（P<0.01）. The rate of renal tubular cell apoptosis in QRXZF
subgroup was lower than that in DKD subgroup（P<0.01）. Conclusion QRXZF effectively improved the renal function，
attenuate the pathological damage and fibrosis of the kidney，inhibit the expression of Caspase-3 and p16 in renal tissues，and
decrease the rate of renal tubular cell apoptosis in DKD rats，suggesting that the mechanism of QRXZF in improving kidney may
be related to inhibiting the aging and apoptosis of kidney cells.
【Key words】 Diabetic nephropathies；Kidney injury；Qingre Xiaozheng formula；Aging；Apoptosis

糖尿病肾病（diabetic kidney disease，DKD）是糖 瘕。前期临床研究发现清热消癥法在降低 DKD 中期患
尿病常见的微血管并发症，也是导致慢性肾病及终末期 者的中医证候评分和尿蛋白排泄量方面具有较好的临
肾脏病（end stage renal disease，ESRD）的主要病因， 床效果 ［15］ 。课题组体内实验表明清热消癥方可以调控
30%~40% 的糖尿病患者会发展为 DKD ［1-2］ 。研究表明， 肠源性脂多糖（lipopolysaccharide，LPS）介导的下游炎
细胞衰老和凋亡是 DKD 发病和进展的重要机制 ［3-4］ 。 症通路，降低炎性因子 toll 样受体 4（toll-like receptor
研究发现 DKD 患者肾小管上皮细胞衰老相关蛋白 p16 4，TLR4）和核因子 κB（nuclear factor kappa-B，NF-
的表达变化与其肾组织损伤程度及肾功能均存在显著关 κB）的表达以及肠源性 LPS 水平，调节 DKD 小鼠的
系 ［5］ 。动物实验发现，DKD 大鼠肾组织中凋亡相关蛋 肠道菌群，降低 DKD 小鼠蛋白尿，抑制 DKD 肾损伤，
白 Caspase-3 mRNA 水平显著增加 ［6］ 。多项研究证实， 发挥肾保护作用 ［16］ 。中药的化学成分多样，靶点繁多，
中医药可以通过抑制肾脏细胞衰老和凋亡，改善 DKD 因此本研究旨在通过动物体内实验进一步明确清热消癥
肾损伤 ［7-13］ 。因此，运用中医药抑制肾脏细胞衰老和 法是否可以通过抑制肾脏细胞衰老和凋亡，改善 DKD
凋亡，可能成为延缓 DKD 进展的新策略。 肾损伤，延缓 DKD 进展。
清热消癥方是北京中医药大学东直门医院肾病专 1 材料与方法
家王耀献教授多年来治疗 DKD 的经验方，他认为“热 1.1 实验动物 2019 年 7—11 月选用 SPF 级健康雄性
邪”是 DKD 发病的主要病因，“伏热致癥”是 DKD 的 SD 大鼠 30 只，8 周龄，体质量（180±20）g，购自维
核心病机，尤其在 DKD 中期，热伏肾络，结为癥瘕， 通利华（北京）实验动物技术有限公司〔SCXK（京）
故立清热消癥法 ［14］ ，以清解内积热邪，消散肾络癥 2012-0001〕。将大鼠饲养于北京中医药大学东直门医