肾安冲剂治疗肾病综合征作用机制的实验研究
摘要
目的：探讨肾安冲剂治疗肾病综合征的作用机制
方法：采用阿霉素（ADR）尾静脉注射制造肾病综合征大鼠模型。将实验大鼠随机分为肾安冲剂组、强的松组、肾安冲剂+强的松组、模型组和正常对照组。各组均从造模后2周开始给药，连续8周。取标本进行24小时尿蛋白定量、血清白蛋白（Alb）、血尿素氮（BUN）、血肌酐（Scr）、血脂、脂蛋白脂酶（LPL）、肾脏病理形态学及Ⅰ、Ⅲ型胶原的检测。
结果：1. 与正常组比较,模型组大鼠24小时尿蛋白定量、血脂水平明显升高,血清白蛋白水平、脂蛋白脂酶活性明显降低,肾小球系膜细胞个数、系膜基质面积和Ⅰ、Ⅲ型胶原面积比均明显增加(均p<0.01).
2.与模型组比较,各治疗组大鼠24小时尿蛋白定量、血脂水平明显降低,血清白蛋白水平、脂蛋白脂酶活性明显升高,肾小球系膜细胞个数、系膜基质面积和Ⅰ、Ⅲ型胶原面积比均明显减少(p<0.05或p<0.01)。
3.肾安冲剂组各检测指标与强的松组比较均有显著性差异(p<0.05或p<0.01),说明肾安冲剂疗效优于强的松。
结论：肾安冲剂能够明显降低24小时尿蛋白定量,升高Alb水平,提高LPL活性,降低血脂水平,抑制肾小球系膜细胞、系膜基质的增生,减少Ⅰ、Ⅲ型胶原的沉积,从而减少了各病理因素的肾损害,最终抑制了ADR肾病大鼠肾组织细胞外基质（ECM）的增生和积聚，延缓了肾小球硬化和肾间质纤维化的进程。
Objective: To study the therapeutic mechanism of SACJ treating nephritic syndrome.
Methods: Nephrotic syndrome(NS) rat models were induced by tail intravenous injection with adriamycin(ADR). The experiment rats were randomly divided into SACJ group, Prednison group, SACJ combined with Prednison group, the model group and normal control group. 2 weeks after the models being made, the admistration of drugs started and lasted for 8 weeks. The content of 24- hour urinary protein, serum albumin, (Alb), BUN, Scr , blood lipid level, activities of lipoprotein lipase (LPL),morphology of renal histology, collagen I and collagen Ⅲ were detected .
Results: 1.The contents of 24-hour urinary protein, lipid level increased and serum albumin level ,activities of LPL decreased significantly in model rats compared with normal rats (p<0.01).The number of mesangial cell, the area of mesangial matrix and the surface area rate of collagenⅠand collagen Ⅲ of model rats were obviously higher than those of normal rats(p<0.01).2. The contents of 24-hour urinary protein and lipid level of all treated group rats were obviously lower than those
of model group rats (P <0.05or p<0.01). Serum albumin level and activities of LPL of all treated group rats were obviously higher than those of model group rats (p<0.05 or p<0.01).The number of mesangial cell, the area of mesangial matrix and the surface area rate of collagenⅠand collagen Ⅲ were significantly reduced in all treated group rats compared with model group rats (p<0.05 or p<0.01).3.There were markedly differences of all test parameters between SACJ group and Prednison group which indicated the therapeutic effect of SACJ was better than that of Prednison for nephritic syndrome.
Conclusion: SACJ decreased the contents of 24-hour urinary protein and lipid level, increased Alb level and activities of LPL, inhibited the proliferation of mesangial matrix and mesangial cell and reduced the deposition of collagen Ⅰ and collagen Ⅲ.So it relieved the lesion of kidney owing to the pathologic agents. SACJ could fundamentally inhibit the ECM accumulation of ADR rats and slow the processes of glomerulosclerosis and renal interstitial fibrosis
方法：采用阿霉素（ADR）尾静脉注射制造肾病综合征大鼠模型。将实验大鼠随机分为肾安冲剂组、强的松组、肾安冲剂+强的松组、模型组和正常对照组。各组均从造模后2周开始给药，连续8周。取标本进行24小时尿蛋白定量、血清白蛋白（Alb）、血尿素氮（BUN）、血肌酐（Scr）、血脂、脂蛋白脂酶（LPL）、肾脏病理形态学及Ⅰ、Ⅲ型胶原的检测。
结果：1. 与正常组比较,模型组大鼠24小时尿蛋白定量、血脂水平明显升高,血清白蛋白水平、脂蛋白脂酶活性明显降低,肾小球系膜细胞个数、系膜基质面积和Ⅰ、Ⅲ型胶原面积比均明显增加(均p<0.01).
2.与模型组比较,各治疗组大鼠24小时尿蛋白定量、血脂水平明显降低,血清白蛋白水平、脂蛋白脂酶活性明显升高,肾小球系膜细胞个数、系膜基质面积和Ⅰ、Ⅲ型胶原面积比均明显减少(p<0.05或p<0.01)。
3.肾安冲剂组各检测指标与强的松组比较均有显著性差异(p<0.05或p<0.01),说明肾安冲剂疗效优于强的松。
结论：肾安冲剂能够明显降低24小时尿蛋白定量,升高Alb水平,提高LPL活性,降低血脂水平,抑制肾小球系膜细胞、系膜基质的增生,减少Ⅰ、Ⅲ型胶原的沉积,从而减少了各病理因素的肾损害,最终抑制了ADR肾病大鼠肾组织细胞外基质（ECM）的增生和积聚，延缓了肾小球硬化和肾间质纤维化的进程。
Objective: To study the therapeutic mechanism of SACJ treating nephritic syndrome.
Methods: Nephrotic syndrome(NS) rat models were induced by tail intravenous injection with adriamycin(ADR). The experiment rats were randomly divided into SACJ group, Prednison group, SACJ combined with Prednison group, the model group and normal control group. 2 weeks after the models being made, the admistration of drugs started and lasted for 8 weeks. The content of 24- hour urinary protein, serum albumin, (Alb), BUN, Scr , blood lipid level, activities of lipoprotein lipase (LPL),morphology of renal histology, collagen I and collagen Ⅲ were detected .
Results: 1.The contents of 24-hour urinary protein, lipid level increased and serum albumin level ,activities of LPL decreased significantly in model rats compared with normal rats (p<0.01).The number of mesangial cell, the area of mesangial matrix and the surface area rate of collagenⅠand collagen Ⅲ of model rats were obviously higher than those of normal rats(p<0.01).2. The contents of 24-hour urinary protein and lipid level of all treated group rats were obviously lower than those
of model group rats (P <0.05or p<0.01). Serum albumin level and activities of LPL of all treated group rats were obviously higher than those of model group rats (p<0.05 or p<0.01).The number of mesangial cell, the area of mesangial matrix and the surface area rate of collagenⅠand collagen Ⅲ were significantly reduced in all treated group rats compared with model group rats (p<0.05 or p<0.01).3.There were markedly differences of all test parameters between SACJ group and Prednison group which indicated the therapeutic effect of SACJ was better than that of Prednison for nephritic syndrome.
Conclusion: SACJ decreased the contents of 24-hour urinary protein and lipid level, increased Alb level and activities of LPL, inhibited the proliferation of mesangial matrix and mesangial cell and reduced the deposition of collagen Ⅰ and collagen Ⅲ.So it relieved the lesion of kidney owing to the pathologic agents. SACJ could fundamentally inhibit the ECM accumulation of ADR rats and slow the processes of glomerulosclerosis and renal interstitial fibrosis
引文
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[2] 毛以林，刘新祥，朱莹. 脾肾双补法治疗原发性肾病综合征48例疗效观察. 湖南中医杂志，2001，17（6）：15-16
[3] Bertani, et al. Adriamycin-induced Nephrotic Syndrome in rat . Lab Invest 1982;46:16
[4] 林志翔，高国华，梅长林，等. 低分子量肝素对阿霉素肾病大鼠脂代谢紊乱的影响. 解放军药学学报，2000；16（6）：321-322
[5] 陈洪宇. 肾病综合征中医证候与病理类型的相关性分析. 浙江中医杂志， 1999，34( 7 )：308-309
[6] 巴元明，王小琴. 邵朝弟教授论难治性肾病综合征发病机理. 中国中医急症，2001，10（4）：222-223
[7] 任克忠. 脾肾双补汤加减治疗肾病综合征的蛋白尿疗效观察.实用中医内科杂志，1996；10（4）：36
[8] 王友富，王建军等. 益肾健脾汤治疗原发性肾病综合征30例.四川中医，2001，19（5）：26-26
[9] 帅明华，温补脾肾法治疗小儿肾病综合征31例.山西中医，2000，16（3）：19
[10] 查良伦，黄士通. 陈锐群，等. 补肾中药拮抗皮质激素所致副反应的实验观察. 上海中医药杂志，1990；（2）：1-3
[11] 章友康，王海燕，朱世乐，等.黄芪和当归治疗三种不同类型肾炎的实验研究. 中华内科杂志，1986，25( 4 )：222
[12] 谷进，潘辑圣，曹红. 黄芪、当归及蛋白质入量对肾病综合征大鼠蛋白质代谢作用的研究. 中华肾脏病杂志，1992，8(4)：226
[13] 李丽英，王海燕，朱世乐，等.黄芪、当归对肾病综合征鼠肝白蛋白的表达作用.中华医学杂志，1995，75(5)：276-279
[14] 陈孟华，李丽英，潘辑圣，等. 黄芪当归对肾病综合征大鼠肌肉蛋白质代谢的
影响 . 中华肾脏病杂志，1997，13(3)：153-155
[15] 李宁军. 李惊子，王海燕，等. 黄芪当归合剂对肾病综合征鼠脂蛋白脂酶和卵磷脂胆固醇酰基转移酶的影响. 中国中西医结合杂志，1999，19(8)，484-486
[16] 俞雷，李惊子，洪建美，等. 黄芪当归合剂降低肾综合征大鼠血脂机制的探讨. 中华肾脏病杂志，1999，15，337-339
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