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目的利用阿霉素肾病模型(daunomycin-induce nephropathy,DMN)研究雷至胶囊的疗效及其对肾组织基质金属蛋白酶(matrix metalloproteinases,MMP)及其抑制物(tissue inhibitor of metalloproteinases,TIMP)的影响。方法实验动物分为正常对照组、模型对照组、贝那普利治疗组、雷公藤多苷治疗组和雷至胶囊治疗组。分别在造模第7天、第28天、第42天和第56天留取血清和尿液标本,观察尿蛋白定量、血清白蛋白、谷丙转氨酶和肾功能等指标的变化;留取肾组织进行光镜、电镜和TGF-β1(转化生长因子-β1)、TIMP-1(金属基质蛋白酶抑制物-1)、和MMP-9(金属基质蛋白酶-9)的逆转录聚合酶链反应(reverse transcription polymerase chain reaction,RT-PCR)。结果①尿蛋白:各治疗组治疗7天尿蛋白减少不明显,但在第28天、42天和56天表现为一定程度的下降,其中雷至胶囊组最为明显,与模型组比较有统计学意义(P<0.05);②血清生化:雷至胶囊治疗组谷丙转氨酶未见明显升高,血清白蛋白水平高于其他各治疗组水平;③肾脏系膜细胞和足细胞的影响:光镜和电镜观察结果显示雷至胶囊治疗组与贝那普利治疗组、雷公藤多苷治疗组和模型组比较系膜细胞增生情况、足细胞融合情况以及系膜基质增生情况均较轻,在尿蛋白明显减少情况下仍然存在与肾脏纤维化相关的肾脏病理进展,表现为程度减轻而不是逆转;④治疗第56天肾脏组织RT-PCR检测发现,雷至胶囊治疗组TGF-β1、TIMP-1表达水平低于其他各治疗组而MMP-9表达水平高于其余各治疗组,组间比较有统计学意义(P<0.05)。结论雷至胶囊对于阿霉素肾病具有较好的治疗作用,能够显著减少蛋白尿,减轻肾组织损伤、保护足细胞结构的完整性和抑制系膜细胞增生。雷至胶囊延缓肾脏纤维化的治疗作用体现在调节与肾脏纤维化相关的肾脏组织转化生长因子、基质金属蛋白酶及其抑制物有关。
Objective To study the effect of Lei Zhi Capsule (DZ) on the expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMP) in renal tissues by using daunomycin-induced nephropathy (DMN). Methods The experimental animals were divided into normal control group, model control group, benazepril treatment group, tripterygium glycosides treatment group and Lei Zhi Capsule treatment group. Serum and urine samples were collected on the 7th, 28th, 42nd and 56th days respectively to observe the change of urinary protein, serum albumin, alanine aminotransferase and renal function; Tissues were subjected to light microscopy, electron microscopy and reverse transcription polymerase chain reaction of TGF-β1 (transforming growth factor-β1), TIMP-1 (matrix metalloproteinase inhibitor-1), and MMP-9 reverse transcription polymerase chain reaction, RT-PCR). Results ① Urine protein: Urine protein decreased significantly in each treatment group on the 7th day but decreased to some extent on the 28th, 42nd and 56th day, especially in Lei Zhi Capsule group, statistically significant compared with the model group (P <0.05). ② Serum biochemistry: No significant increase in alanine aminotransferase (ALT) and serum albumin level were found in Lei Zhi Capsule treatment group. (3) The effect of mesangial cells and podocytes: The results of electron microscopy showed that the mesangial cell hyperplasia, podocyte fusion and mesangial matrix hyperplasia were lighter in Lei Zhi Capsule treatment group and benazepril treatment group and tripterygium glycosides treatment group and model group. Protein expression was significantly reduced renal nephropathy related to renal fibrosis is still pathological progress, showed a degree of reduction rather than reverse; ④ treatment on the 56th day renal tissue RT-PCR detection, Lei Zhi Capsule treatment group TGF-β1, TIMP-1 The expression level of MMP-9 was lower than other treatment groups, and the expression level of MMP-9 was higher than other treatment groups. There was significant difference between the two groups (P <0.05). Conclusion Lei Zhi Capsule has a good therapeutic effect on doxorubicin nephropathy, can significantly reduce proteinuria, reduce renal tissue damage, protect the integrity of podocyte structure and inhibit mesangial cell proliferation. Lei Zhi capsules delay the treatment of renal fibrosis in the role of regulation in renal tissue associated with renal fibrosis, transforming growth factor, matrix metalloproteinases and their inhibitors.