【作者】 周珂；

【导师】 蔡光先；

【作者基本信息】 湖南中医药大学 ， 中医内科学， 2011， 博士

【摘要】 目的：观察超微黑地黄汤：①对慢性肾脏病(CKD)3期患者的临床疗效；②对单侧输尿管结扎大鼠行为、体态、体重及其肾脏组织病理的影响；③对单侧输尿管结扎大鼠肾组织细胞凋亡的影响；④对单侧输尿管结扎大鼠FN、ColⅣ、TGF-β1的调节作用。方法：临床研究—随机将60例CKD3期患者分为超微组和尿毒清组,比较两组患者治疗前后血红蛋白、血肌酐、尿素氮、24小时尿蛋白定量的变化。动物实验—将40只单侧输尿管结扎(UU0)SD大鼠按照完全随机的方法分为空白组、假手术组、模型组、超微组和尿毒清组,干预14天后,观察下列指标：①单侧输尿管结扎大鼠行为、体态、体重及其肾脏组织病理学；②采用免疫组织化学方法检测各组大鼠肾组织Bcl-2、Bax,并与细胞凋亡原位检测(TUNEL法)进行对比；③各组大鼠血肌酐、尿素氮、24小时尿蛋白定量；④采用酶联免疫吸附法(ELISA)及其免疫组织化学方法检测各组大鼠血清FN、ColⅣ、TGF-β1的浓度值。结果：超微组和尿毒清组总有效率相近(P>0.05)。对血肌酐、尿素氮和24小时尿蛋白定量均有改善作用(P<0.05),但对血红蛋白无明显改善作用(P>0.05),而两组血肌酐的改善无统计学差异(P>0.05),尿素氮的改善尿毒清组优于超微组(P<0.05),而24小时尿蛋白定量的改善情况是超微组优于尿毒清组(P<0.05)。干预后模型组行为、体态及体重的改变均明显异于其他组大鼠,而病理改变最严重。超微组大鼠肾功能和尿蛋白定量均明显优于模型组(P<0.05),与尿毒清具有相近疗效(P>0.05)；超微组和尿毒清组大鼠血清中所含的FN、ColⅣ浓度相近(P>0.05),而低于模型组大鼠(P<0.05)；超微组和尿毒清组大鼠Bcl-2均高于模型组(P<0.05),而Bax、TGFβ1均低于模型组(P<0.05)。TUNEL法检测的细胞凋亡显示超微组与尿毒清组的细胞凋亡数少于模型组(P<0.05)。结论：本研究结果证明：①超微黑地黄汤治疗脾肾气虚型CKD3期患者,安全有效,且疗效与尿毒清相似；②超微黑地黄汤对UUO大鼠的行为、体态、体重及肾脏组织病理有明确改善作用；③超微黑地黄汤有降低UUO大鼠24小时尿蛋白定量,改善肾功能的作用；④超微黑地黄汤的临床疗效与其能够减少肾组织中肾小管上皮细胞的凋亡,抑制FN、ColIV、TGF-β1的表达有关。更多还原

【Abstract】 Objective:To investigate①the clinical effect of super-micro Black Dihuang decoction on Chronic Kidney Disease (CKD) 3 degree.②the influence of super-micro Black Dihuang decoction on behavior, posture, weight and pathological kidney of UUO rats.③the effect of super-micro Black Dihuang decoction on apoptosis and renal organization Bcl-2、Bax of Unilateral Ureteral Obstruction (UUO) rats.④the effect of super-micro Black Dihuang decoction on serum FN、ColⅣ、TGFβ1 of Unilateral Ureteral Obstruction (UUO) rats.Methods:Clinical study:60 CKD 3 degree patients were divided randomly into the Super-micro group and Niaoduqing group,compared the 24-hour urinary protein quantitative,serum creatinine, urea nitrogen and the efficacy before and after treatment. Animal experiment:40 Unilateral Ureteral Obstruction (UUO) SD rats were randomized into Control group, Sham operation group, Model group, Super-micro group and Niaoduqing group. After 14 days, next indicators of each group rats were detected:①behavior, posture, weight and pathological kidney of UUO rats.②the concentration of Bcl-2 and Bax with immunohistochemistry method, and compared with the apoptosis of renal organization with TUNEL method③the rat kidney morphology of each group.④the serum creatinine, urea nitrogen and 24-hour urine protein of each group.⑤the concentration of FN、ColⅣin serum with enzyme-linked timmunosorbent assay (ELISA) method, and the concentration of TGFβ1 with immunohistochemistry method.Results:The total effective of Super-micro group and the Niaoduqing group is similar (P>0.05). Both two groups were improved On serum creatinine, urea nitrogen and 24-hour urine protein quantitative (P<0.05), but no difference on hemoglobin and no significant difference between Super-micro group and the Niaoduqing group in the improvement of serum creatinine (P>0.05), urea nitrogen to improve in Niaoduqing group is better than that of Super-micro group (P<0.05), while the 24-hour urinary protein of Super-micro group to improve was better than Niaoduqing group (P<0.05). The behavior, posture and weight changes of model group were significantly different from the other group, In pathology, Super-micro group was simila with Niaoduqing group, but significantly different from the model group. Super-micro Black Dihuang decoction on renal function and urinary protein were clearly improved effect (P<0.05). Experimental study also was found a similar effect (P> 0.05) between Super-micro rats group and Niaoduqing rats group, while serum FN、ColⅣconcentrations of Super-micro Black Dihuang decoction were found similar levels as those of Niaoduqing (P> 0.05), but much lower than that of the model group (P<0.05). Bcl-2 of Super-micro group and Niaoduqing group were higher than model group (P<0.05), while Bax and TGFβ1 of Super-micro group and Niaoduqing group were lower than the model group (P<0.05). The apoptosis of Super-micro group and Niaoduqing group are lower than that of the model group (P <0.05).Conclusion:①Super-micro Black Dihuang decoction group with Spleen and Kidney deficiency type can be treated safely and effectively, whose effect is similar with that of Niaoduqing.②The behavior, body weight and renal pathology of Super-micro Black Dihuang decoction group has a clear role.③Super-micro Black Dihuang decoction can reduce the 24-hour urine protein, improve kidney function.④Supermicro Black Dihuang decoction can inhibit FN, ColⅣ, TGFβ1, which can reduce the apoptosis of renal.更多还原