“益气排毒方”治疗慢性肾功能不全的实验研究
发布时间：2018-08-29 18:05
【摘要】：慢性肾功能不全又称慢性肾脏病,是以代谢产物潴留,水、电解质、酸碱平衡失调,全身各系统受累为主要表现的临床综合征。随着医学的进步和检验方法和技术的不断提高,慢性肾功能不全的发病率逐年升高。许多慢性肾功能不全患者由于治疗不及时、不恰当,导致体内毒素蓄积,增加对肾脏功能的损害,从而迅速进入尿毒症期。尿毒症毒素蓄积,严重危害患者的生活和健康,降低生活质量,庞大的治疗费用更是给家庭和社会带来巨大的负担。所以,探索治疗慢性肾功能不全的新方法非常有临床意义。 益气排毒方是清远市中医院欧阳永红教授30余年临床经验的总结,主要应用于治疗有肾功能损害临床表现,实验室指标血尿素氮、肌酐升高的患者,即慢性肾功能不全的病人,收入清远市中医院协定处方,在改善患者精神状况、贫血、四肢乏力等症状,降低血肌酐、尿素氮、蛋白尿、尿液潜血等方面效果显著。1992年欧阳永红教授提出使用“益气泻浊”法治疗慢性肾功能不全,2011年王瑞等研究发现益气排毒方对维持性血液透析患者的微炎症状态有干预作用,可降低微炎症状态对机体的损害,改善营养不良；2012年“益气排毒方治疗慢性肾功能不全脾肾气虚证的临床研究”已列为广东省中医药管理局的课题。为了阐明益气排毒方改善慢性肾功能不全的机理,我们通过动物实验,论证益气排毒方在改善大鼠一般情况,保护大鼠肾功能,调节血脂和钙磷代谢,改善贫血等作用,并尝试探讨方剂的作用机理。 目的： 采用腺嘌呤毒害大鼠肾脏,建立慢性肾功能不全大鼠模型,观察益气排毒方对慢性肾功能不全大鼠一般情况的影响,对血肌酐、尿素氮、血红蛋白、血脂、血液钙磷代谢等指标的影响,并观察肾脏病理改变。对比尿毒清颗粒对大鼠肾脏保护作用,分析作用机制,探讨益气排毒方纠正慢性肾衰竭的作用机理。 方法： 选取180-220gSPF级wistar大鼠40只,雌雄各半,给予固体饮食和自由饮水,规律喂养一周后,随机分为4组,每组10只,选取一组为正常对照组,其余30只为慢性肾功能不全造模组,给予100mg/kg/d腺嘌呤灌胃,连续喂养21天造模成功后,选取造模成功的大鼠,按照体重大小重新排序,按照计算机产生的随机数字将已造模的大鼠,随机分配为三组：模型对照组、尿毒清组、益气排毒方组,根据正常成人和大鼠体重换算,其中尿毒清组按照按照4.0g/kg的比例,灌胃；益气排毒方组按照23.38ml/kg来灌胃,平均每只大鼠约4ml药液,连续给药28天。麻醉,取血,检测血肌酐、尿素氮、血脂、电解质等指标,观察双肾病理改变。 结果： 1、造模结果：造模后,造模组大鼠与正常组大鼠相比,精神状态差,反应迟钝,毛色灰白,活动减少。体重与正常组相比,差异有统计学意义(P0.05)；但造模组之间,体重无显著差异(P0.05)。随机抽取一只造模大鼠,心脏取血,检验肾功能提示,血肌酐和尿素氮显著升高,肾脏病理解剖见肾脏体积增大,颜色淡白,呈现“大白肾”,HE染色见肾小球、肾小管、肾间质部分组织结构损坏。 2、治疗结果： (1)一般情况。灌服益气排毒方的慢性肾功能不全大鼠,一般情况优于模型对照组,大鼠精神状态好,反应敏捷,进食量多,毛发较有光泽,但尚未达到正常水平；与尿毒清组相比,益气排毒方组大鼠与其精神状态、反应灵敏度相当,但毛发较有光泽,说明益气排毒方组在改善CRF大鼠一般状况方面稍优于尿毒清组,但无差异。 (2)改善体重方面。正常对照组、尿毒清组和益气排毒方组体重均逐渐上升,正常组上升幅度较大,尿毒清组上升较慢,空白组大鼠在实验第二周体重达到峰值,随即开始下降进一步加重。实验后,益气排毒方组与正常对照组、模型对照组和尿毒清组相比差异均具有统计学意义(P0.05)；尿毒清组与模型对照组相比体重无差异(P0.05),与益气排毒方组相比有差异(P0.05),说明尿毒清在改善CRF大鼠体重方面效果不及益气排毒方。 (3)对肾功能的影响：益气排毒方与模型对照组相比较,血肌酐和尿素氮的降低均有统计学意义(P0.05),与正常组相比两指标均显著升高(P0.01),益气排毒方与尿毒清相比血肌酐显著降低(P0.05),尿素氮差异无统计学意义(P0.05)。(4)对血脂的影响：益气排毒方组在TG和TC上与正常对照组相比,均无差异(P0.05),而与模型对照组显著升高(P0.01)。尿毒清组较正常对照组显著降低(P0.05),较益气毒方组显著升高(P0.05)。 (5)对血清钙、磷的影响：益气排毒方组血清钙与正常对照组相比无显著差异(P0.05),与模型对照组比有显著差异(P0.01),与尿毒清相比显著升高(P0.05)；调节血磷方面,益气排毒方与正常对照组、模型对照组和尿毒清组相比,差异均无统计学意义(P0.05)。 (6)对血红蛋白的影响：益气排毒方组血红蛋白与正常组无明显差异(P0.05),与模型对照组和尿毒清组相比明显升高(P0.01)。在红细胞计数方面,益气排毒方组与正常对照组、模型对照组和尿毒清组相比,均有较大差异(P0.01)。 (7)肾脏病理观察： ①肾脏外观观察上,益气排毒方组肾脏肿胀、薄膜增厚程度较模型对照组轻,表面颜色较模型对照组深,说明该方具有保护肾功能的作用。 ②对肾重/体重比的影响。腺嘌呤至大鼠肾功能衰竭,出现肾脏肿胀,肾重/体重比值明显升高,与正常组比较具有显著差异(P0.01),益气排毒方能减轻肾脏损害水肿的进程,降低肾重/体重比值(P0.01),这种作用优于尿毒清组(P0.05)。 ③HE染色观察：益气排毒方组大鼠肾脏有少量肾小管上皮细胞脱落,部分肾小管扩张,部分可见深黄色结晶,其肾脏损害的表现较空白组轻。 结论： 益气排毒方对腺嘌呤所致慢性肾功能不全大鼠具有改善大鼠体重降低,改善一般情况,改善肾功能,调节血脂,纠正贫血,纠正钙磷代谢紊乱的作用。在降低血肌酐、血脂和调节钙磷代谢方面,与尿毒清相比疗效更好,具有良好的发展前景,但其具体作用机制还有待进一步深入探讨。
[Abstract]:Chronic renal insufficiency, also known as chronic kidney disease, is a clinical syndrome characterized by metabolite retention, water, electrolyte, acid-base imbalance and systemic involvement. Untimely and inappropriate treatment will lead to accumulation of toxins in the body and increase the damage to kidney function, thus rapidly entering the uremic period. The accumulation of uremic toxins will seriously endanger the life and health of patients and reduce the quality of life. The huge cost of treatment is a huge burden to families and society. Therefore, exploring the treatment of chronic renal failure. The whole new method is very clinically significant.
Yiqi Paidu Recipe is a summary of Professor Ouyang Yonghong's clinical experience in more than 30 years in Qingyuan Hospital of Traditional Chinese Medicine. It is mainly used in the treatment of patients with renal impairment and elevated serum urea nitrogen and creatinine, that is, patients with chronic renal insufficiency. In 1992, Professor Ouyang Yonghong proposed to use the method of "supplementing Qi and reducing turbidity" to treat chronic renal insufficiency. In 2011, Wang Rui and other studies found that Yiqi Paidu Recipe can intervene in maintaining the Micro-inflammatory State of hemodialysis patients and reduce micro-inflammation. In order to clarify the mechanism of Yiqi Paidu Recipe in improving chronic renal insufficiency, we demonstrated that Yiqi Paidu Recipe is improving the chronic renal insufficiency through animal experiments. In general, it can protect the renal function of rats, regulate the metabolism of blood lipids, calcium and phosphorus, improve anemia and so on.
Objective:
Adenine was used to poison the kidney of rats to establish the model of chronic renal insufficiency. The effects of Yiqi Paidu Recipe on the general condition of rats with chronic renal insufficiency, the indexes of serum creatinine, urea nitrogen, hemoglobin, blood lipids, blood calcium and phosphorus metabolism were observed, and the pathological changes of kidney were observed. To analyze the mechanism of action and explore the mechanism of Yiqi detoxification formula in correcting chronic renal failure.
Method:
Forty Wistar rats of 180-220 g SPF grade were divided into four groups randomly after one week of regular feeding. One group was normal control group, the other 30 were chronic renal insufficiency model group. Adenine was given 100mg/kg/d by gastric lavage. After 21 days of successful modeling, the rats were fed with solid diet and free drinking water. Rats were randomly divided into three groups: model control group, Niao Du Qing group, Yiqi Paidu Fang group. The rats were converted according to the weight of normal adults and rats. The rats in Niu Du Qing group were given intragastric administration according to the ratio of 4.0g/kg, and the rats in Yiqi Paidu Fang group were given intragastric administration according to 23.38ml/kg. To the stomach, an average of about 4 ml of liquid per rat, continuous administration for 28 days. Anesthesia, blood samples, serum creatinine, urea nitrogen, blood lipids, electrolytes and other indicators to observe the pathological changes of the two kidneys.
Result:
1. Modeling results: Compared with the normal group, the rats in the model group had worse mental state, sluggish reaction, grey-white hair and less activity. There was a significant difference in body weight (P 0.05), but there was no significant difference in body weight between the model group (P 0.05). Creatinine and urea nitrogen increased significantly, renal pathological anatomy showed enlarged renal volume, pale color, showing a "large white kidney", HE staining showed glomerulus, renal tubules, renal interstitial tissue damage.
2, treatment outcome:
(1) General condition. Rats with chronic renal insufficiency who were given Yiqi Paidu Recipe were generally better than those in the model control group. Rats in Yiqi Paidu Recipe group had better mental state, quick reaction, more food intake, glossy hair, but not yet reached the normal level. The luster showed that Yiqi Paidu Fang group was slightly better than Niaoduqing group in improving the general condition of CRF rats, but there was no difference.
(2) Improvement of body weight. In the normal control group, the body weight of Niaoduqing group and Yiqi Paidu Fang group increased gradually, while that of the normal group increased greatly, and that of the Niaoduqing group increased slowly. In the blank group, the body weight of the rats reached the peak value in the second week of the experiment, and then began to decline further. After the experiment, the Yiqi Paidu Fang group and the normal control group, the model control group and the model control group. Compared with the model control group, there was no difference in body weight between the two groups (P 0.05), and there was a difference between the two groups (P 0.05), indicating that the effect of Niaoduqing on improving the body weight of CRF rats was not as good as that of Yiqi Paidu Recipe.
(3) Effect on kidney function: Compared with model control group, Yiqi Paidu Recipe had statistical significance in reducing serum creatinine and urea nitrogen (P 0.05), both indexes were significantly higher than normal group (P 0.01), Yiqi Paidu Recipe had significantly lower serum creatinine (P 0.05) and no significant difference in urea nitrogen (P 0.05). Effect: Compared with the normal control group, the TG and TC of the Yiqi Paidu Formula group had no difference (P 0.05), but increased significantly (P 0.01) compared with the model control group.
(5) Effect of Yiqi Paidu Recipe on serum calcium and phosphorus: There was no significant difference between Yiqi Paidu Recipe group and normal control group (P Academic meaning (P0.05).
(6) Effect of Yiqi Paidu Recipe on hemoglobin: There was no significant difference between Yiqi Paidu Recipe group and normal group (P 0.05), but it was significantly higher than model control group and Niaoduqing group (P 0.01). In red blood cell count, Yiqi Paidu Recipe group was significantly different from normal control group, model control group and Niaoduqing group (P 0.01).
(7) renal pathology:
(1) Kidney appearance observation showed that Yiqi Paidu Recipe could protect the kidney function because of the swelling of the kidney, the thickness of the membrane was lighter than that of the model control group, and the surface color was darker than that of the model control group.
(2) Effect on the ratio of kidney weight to body weight.Adenine-induced renal failure in rats resulted in kidney swelling and the ratio of kidney weight to body weight increased significantly compared with the normal group (P 0.01). Yiqi Paidu Recipe could reduce the process of kidney edema and the ratio of kidney weight to body weight (P 0.01), which was better than that of Uremic Qing (P 0.05).
(3) HE staining observation: the kidney of rats in Yiqi Paidu Recipe group showed a small amount of renal tubular epithelial cell exfoliation, some renal tubules dilatation, some dark yellow crystals, and the renal damage was lighter than the blank group.
Conclusion:
Yiqi Paidu Recipe can improve the weight loss of rats with chronic renal insufficiency induced by adenine, improve general conditions, improve renal function, regulate blood lipids, correct anemia, correct calcium and phosphorus metabolism disorders. However, its specific mechanism remains to be further explored.
【学位授予单位】：广州中医药大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R277.5
本文编号：2211991
[Abstract]:Chronic renal insufficiency, also known as chronic kidney disease, is a clinical syndrome characterized by metabolite retention, water, electrolyte, acid-base imbalance and systemic involvement. Untimely and inappropriate treatment will lead to accumulation of toxins in the body and increase the damage to kidney function, thus rapidly entering the uremic period. The accumulation of uremic toxins will seriously endanger the life and health of patients and reduce the quality of life. The huge cost of treatment is a huge burden to families and society. Therefore, exploring the treatment of chronic renal failure. The whole new method is very clinically significant.
Yiqi Paidu Recipe is a summary of Professor Ouyang Yonghong's clinical experience in more than 30 years in Qingyuan Hospital of Traditional Chinese Medicine. It is mainly used in the treatment of patients with renal impairment and elevated serum urea nitrogen and creatinine, that is, patients with chronic renal insufficiency. In 1992, Professor Ouyang Yonghong proposed to use the method of "supplementing Qi and reducing turbidity" to treat chronic renal insufficiency. In 2011, Wang Rui and other studies found that Yiqi Paidu Recipe can intervene in maintaining the Micro-inflammatory State of hemodialysis patients and reduce micro-inflammation. In order to clarify the mechanism of Yiqi Paidu Recipe in improving chronic renal insufficiency, we demonstrated that Yiqi Paidu Recipe is improving the chronic renal insufficiency through animal experiments. In general, it can protect the renal function of rats, regulate the metabolism of blood lipids, calcium and phosphorus, improve anemia and so on.
Objective:
Adenine was used to poison the kidney of rats to establish the model of chronic renal insufficiency. The effects of Yiqi Paidu Recipe on the general condition of rats with chronic renal insufficiency, the indexes of serum creatinine, urea nitrogen, hemoglobin, blood lipids, blood calcium and phosphorus metabolism were observed, and the pathological changes of kidney were observed. To analyze the mechanism of action and explore the mechanism of Yiqi detoxification formula in correcting chronic renal failure.
Method:
Forty Wistar rats of 180-220 g SPF grade were divided into four groups randomly after one week of regular feeding. One group was normal control group, the other 30 were chronic renal insufficiency model group. Adenine was given 100mg/kg/d by gastric lavage. After 21 days of successful modeling, the rats were fed with solid diet and free drinking water. Rats were randomly divided into three groups: model control group, Niao Du Qing group, Yiqi Paidu Fang group. The rats were converted according to the weight of normal adults and rats. The rats in Niu Du Qing group were given intragastric administration according to the ratio of 4.0g/kg, and the rats in Yiqi Paidu Fang group were given intragastric administration according to 23.38ml/kg. To the stomach, an average of about 4 ml of liquid per rat, continuous administration for 28 days. Anesthesia, blood samples, serum creatinine, urea nitrogen, blood lipids, electrolytes and other indicators to observe the pathological changes of the two kidneys.
Result:
1. Modeling results: Compared with the normal group, the rats in the model group had worse mental state, sluggish reaction, grey-white hair and less activity. There was a significant difference in body weight (P 0.05), but there was no significant difference in body weight between the model group (P 0.05). Creatinine and urea nitrogen increased significantly, renal pathological anatomy showed enlarged renal volume, pale color, showing a "large white kidney", HE staining showed glomerulus, renal tubules, renal interstitial tissue damage.
2, treatment outcome:
(1) General condition. Rats with chronic renal insufficiency who were given Yiqi Paidu Recipe were generally better than those in the model control group. Rats in Yiqi Paidu Recipe group had better mental state, quick reaction, more food intake, glossy hair, but not yet reached the normal level. The luster showed that Yiqi Paidu Fang group was slightly better than Niaoduqing group in improving the general condition of CRF rats, but there was no difference.
(2) Improvement of body weight. In the normal control group, the body weight of Niaoduqing group and Yiqi Paidu Fang group increased gradually, while that of the normal group increased greatly, and that of the Niaoduqing group increased slowly. In the blank group, the body weight of the rats reached the peak value in the second week of the experiment, and then began to decline further. After the experiment, the Yiqi Paidu Fang group and the normal control group, the model control group and the model control group. Compared with the model control group, there was no difference in body weight between the two groups (P 0.05), and there was a difference between the two groups (P 0.05), indicating that the effect of Niaoduqing on improving the body weight of CRF rats was not as good as that of Yiqi Paidu Recipe.
(3) Effect on kidney function: Compared with model control group, Yiqi Paidu Recipe had statistical significance in reducing serum creatinine and urea nitrogen (P 0.05), both indexes were significantly higher than normal group (P 0.01), Yiqi Paidu Recipe had significantly lower serum creatinine (P 0.05) and no significant difference in urea nitrogen (P 0.05). Effect: Compared with the normal control group, the TG and TC of the Yiqi Paidu Formula group had no difference (P 0.05), but increased significantly (P 0.01) compared with the model control group.
(5) Effect of Yiqi Paidu Recipe on serum calcium and phosphorus: There was no significant difference between Yiqi Paidu Recipe group and normal control group (P Academic meaning (P0.05).
(6) Effect of Yiqi Paidu Recipe on hemoglobin: There was no significant difference between Yiqi Paidu Recipe group and normal group (P 0.05), but it was significantly higher than model control group and Niaoduqing group (P 0.01). In red blood cell count, Yiqi Paidu Recipe group was significantly different from normal control group, model control group and Niaoduqing group (P 0.01).
(7) renal pathology:
(1) Kidney appearance observation showed that Yiqi Paidu Recipe could protect the kidney function because of the swelling of the kidney, the thickness of the membrane was lighter than that of the model control group, and the surface color was darker than that of the model control group.
(2) Effect on the ratio of kidney weight to body weight.Adenine-induced renal failure in rats resulted in kidney swelling and the ratio of kidney weight to body weight increased significantly compared with the normal group (P 0.01). Yiqi Paidu Recipe could reduce the process of kidney edema and the ratio of kidney weight to body weight (P 0.01), which was better than that of Uremic Qing (P 0.05).
(3) HE staining observation: the kidney of rats in Yiqi Paidu Recipe group showed a small amount of renal tubular epithelial cell exfoliation, some renal tubules dilatation, some dark yellow crystals, and the renal damage was lighter than the blank group.
Conclusion:
Yiqi Paidu Recipe can improve the weight loss of rats with chronic renal insufficiency induced by adenine, improve general conditions, improve renal function, regulate blood lipids, correct anemia, correct calcium and phosphorus metabolism disorders. However, its specific mechanism remains to be further explored.
【学位授予单位】：广州中医药大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R277.5
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