生物节律紊乱影响糖尿病肾病大鼠“气阴亏虚”病机的初步探讨

Preliminary mechanism study of disruption of chronobiological rhythm promoting diabetic nephropathy through “deficiency of Qi and Yin” pathogenesis: verification in animal experiments

[目的]探讨生物节律紊乱对糖尿病肾病大鼠"气阴亏虚"病机的影响。[方法]选用健康SD雄性大鼠64只,随机分为4组,每组16只,分别为:空白组、生物节律紊乱组、糖尿病肾病(DN)组、DN生物节律紊乱组。DN组及DN生物节律紊乱组为小剂量多次腹腔注射链脲佐菌素(STZ)溶液,高脂饲料喂养建立。复制大鼠糖尿病肾病模型后,生物节律紊乱组、DN生物节律紊乱组同时改变光照诱导为生物节律紊乱模型。实验结束后,观察大鼠饮水量、尿量及体质量变化情况,检测大鼠模型血液中的血糖值、24h尿蛋白定量及环磷酸腺苷(cAMP)与环磷酸鸟苷(cGMP)的表达水平与比值;大鼠肾脏病理切片苏木精-伊红(HE)染色、过碘酸雪夫(PAS)染色观察病理改变。[结果]1)与空白组相比,DN组与DN生物节律紊乱组的饮水量、尿量、血糖值、24h尿蛋白定量明显增多(P<0.01);DN组cAMP含量降低(P<0.05),DN生物节律紊乱组cGMP含量升高(P<0.05),cAMP/cGMP比值降低(P<0.01)。2)与DN组相比,DN生物节律紊乱组饮水量、尿量、血糖值明显下降(P<0.01),24h尿蛋白定量明显增多(P<0.01),肾脏病理损害严重;cGMP的含量升高,cAMP与cGMP的比值降低(P<0.05)。[结论]生物节律紊乱可通过对机体耗气伤阴,促进糖尿病肾病进程。

[Objective] To observe the effect of ＂deficiency of Qi and Yin＂ pathogenesis in chronobiological rhythm disordered diabetic nephropathy rats. [Methods] Sixty-four Male Sprague Dawley（SD） rats were randomly divided into normal control group, chronobiology disorder group, diabetic nephropathy（DN） group, and DN chronobiology disorder group（ n = 16 in each group）. DN rats and chronobiology disorder DN rats were injected intraperitoneally with a low dose streptozotocin（STZ） dissolved in saline sodium citrate（SSC） repeatly and fed with high-fat food. After establishing DN models in eight weeks, chronobiology disorder were induced by changing illumination rhythm in chronobiology disorder rats and DN chronobiology disorder rats for six weeks. The drinking volume, urine volume and the change of weight were recorded. The blood glucose,24 h urinary protein excretion, the ratio of c AMP and c GMP were measured,then, to observe the pathological changes of the kidney, histology of the kidney sections stained with hematoxylin-eosin and Periodic Acid-Schiff were used.[Results] ①Compared with those in control group, the drinking volume, urine volume, blood glucose,24 h urinary protein excretion significantly increased in DN group and DN chronobiology disorder group（P〈0.01）, the expression of c AMP decreased in DN group（P〈0.05, the expression of c GMP increased（P〈0.05） and the ratio of c AMP and c GMP significantly decreased（P 〈0.01） in DN chronobiology disorder group. ② In contrast to the mice in DN group, the drinking volume, urine volume and blood glucose significantly decreased and 24 h urinary protein excretion significantly increased（P〈0.01）,the results of renal pathological showed developed renal lesions, the expression of c GMP increased and the ratio of c AMP and c GMP decreased（ P 〈 0. 05） in DN chronobiology disorder group.[Conclusion] The disruption of chronobiological rhythm may promote diabetic nephropathy through ＂deficiency of Qi and Yin＂ pathogenesis.