摘要
目的：糖尿病肾病(DN)是DM最常见的并发症,也是糖尿病患者的主要死亡原因之一。DN在我国终未期肾衰患者近年来已升至15%,且随生活水平提高而有上升趋势。肾小球硬化是DN的微血管病并发症,其病情发展最终导致肾功能衰竭。近年来提出的糖尿病炎症发病学说被认为是DM病因和发病机制研究的重大进展,炎症能引起DN,并在DN进展的整个过程中起重要作用,抗炎治疗有望成为延缓DN慢性进展的有效方法。本研究以中医理论为指导,旨在探讨益气养阴、祛瘀生新法(糖肾安)治疗DN的临床疗效,并观察其对DN患者血清炎症因子超敏C反应蛋白(hs-CRP)、肿瘤坏死因子(TNFα)、白细胞介素-6(IL-6)等的影响,冀能寻找治疗DN有效方药,为中医药防治DN提供新的理论与临床资料。
方法：采用随机、对照的原则,按照纳入标准将45例DN患者按纳入先后顺序2：1比例随机分为治疗组30例,对照组15例。两组均予①控制血糖、控制血压、降血脂、优质低蛋白饮食、纠正水、电解质、酸碱平衡紊乱、防治并发感染等治疗。治疗组在此基础上配合益气养阴、祛瘀生新中药复方糖肾安(黄芪、太子参、玉米须各30g,桑椹子20g、当归10 g、玄参15g,川芎10g、熟大黄6～10g,冬虫夏草孢子粉3g)治疗,每天1剂,水煎分2次服。2组疗程均为8周。观察患者临床疗效及临床症状积分变化情况,检测患者治疗前后空腹血糖、肾功能(BUN、Cr)、血脂(Chol、TG)、24小时尿蛋白定量、血清TNFα、IL-6、hs-CRP的变化。
结果：
①治疗后两组症状积分均较治疗前明显降低,差异有非常显著性意义(P<0.01),表明两组均可改善DN临床症状。治疗组对改善临床症状积分更为显著,与对照组比较,差异有非常显著性意义(P<0.01)；两组症状积分治疗前后差值比较,差异有非常显著性意义(P<0.01)。
②治疗组治疗后肾功能指标BUN、Cr均有不同程度改善,与治疗前比较,差异有显著性意义(P<0.05)；与对照组治疗后比较,差异有显著性意义(P<0.05)。
③两组治疗后FBG均有明显下降,与治疗前比较,差异均有非常显著性意义(P<0.01)；治疗后两组间比较,差异无显著意义(P>0.05),提示两组血糖在整个治疗观察中均控制在规定范围内。治疗后两组24h尿蛋白定量均有不同程度的下降,与治疗前比较,差异有显著性或非常显著性意义(P<0.05,P<0.01)；治疗组下降明显优于对照组,差异有显著性意义(P<0.05)。
④治疗后两组TC, TG值均有不同程度的下降,与治疗前比较,差异有显著性或非常显著性意义(P<0.05,P<0.01)；且治疗组下降明显明优于对照组,差异有显著性意义(P<0.05)。
⑤治疗组与对照组治疗前血清Hs-CRP水平均异常增高,两组比较无显著性差异(P>0.05)。治疗后两组Hs-CRP值均有明显下降,与治疗前比较,差异均有非常显著性意义(P<0.01)；且治疗组下降明显明优于对照组,差异有非常显著性意义(P<0.01)。对照组、治疗组疗前血清IL-6、TNF-a水平均异常增高,两组分别比较均无显著性差异(P>0.05)。治疗后治疗组IL-6、TNF-a水平均明显下降,与治疗前比较,差异有显著性意义(P<0.05)；与对照组治疗后比较,差异亦有显著性意义(P<0.05)。对照组上述指标治疗后虽有下降趋势,但前后比较,差异无显著性(P>0.05)。
⑥经8周治疗后,治疗组显效8例,有效18例,无效4例,总有效率为86.7.0%,对照组显效1例,有效7例,无效7例,总有效率为53.3%。2组总有效率比较,差异有显著性意义(P<0.05)。
结论：
1.以益气养阴,祛瘀生新法组方的中药复方(糖肾安)可改善DN患者的临床症状,降低患者气阴两虚、瘀血阴络证的症状积分,并可降低患者24小时尿蛋白,改善其肾功能、血脂代谢。
2.糖尿病肾病血清Hs-CRP、TNF-α、IL-6水平异常增高,益气养阴,祛瘀生新中药复方可明显下调DN患者炎症因子Hs-CRP、TNF-α、IL-6的水平,改善DN微炎症状态
3.益气养阴、祛瘀生新中药复方治疗临床期DN具有较好的疗效,可通过多环节延缓DN肾小球硬化的病程进展,其中下调炎症因子水平,抑制或改善炎症反应可能是该法抗DN肾小球硬化的主要机理之一。
Objective:Diabetic nephropathy (DN) is the most common complications of DM, diabetes is one of the major causes of death in patients with DN in Chinese patients with end-stage renal failure in recent years has risen to 15%. in recent years with the high living standard DN has the tend on the increase. Glomerular sclerosis is the micro-vascular complications of DN and the progression of the disease leading to renal failure. The incidence of diabetes have been proposed theory is considered inflammatory etiology and pathogenesis of DM significant progress, inflammation can lead to DN, and DN progress in the whole process played an important role in the anti-inflammatory treatment is expected to be slow progress by one of the effective methods to chronic DN. In this study, Chinese medicine theory, to explore the tonificating qi and nourishing yin, removing blood stasis of Chinese medicine (kang shen fang) the clinical efficacy of treatment of DN and DN were observed on serum levels of high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNFα), interleukin-6 (IL-6) and other effects, aiming to find an effective prescription treatment of DN and the Chinese medicine in prevention and treatment of DN to provide ideas.
Methods:A randomized, controlled the principle of inclusion criteria to 45 patients according to DN in patients with a 2:1 ratio were randomly divided into treatment group 30 cases and control group 15 cases. Two groups correspondingly control of blood glucose, blood pressure, blood fat, high-quality low-protein diet, correcting water, electrolyte, acid-base balance disorders, prevention treatment of complicated infections. On this basis, the treatment group use of tonificating qi and nourishing yin, removing blood stasis and regeneration promoting of Chinese medicine (kang shen fang) (Astragalus memeranaceus(Fisch), Pseudostellaria heterophylla(Miq), zea mays L each one 30 gram, Morus alba L 20 gram, Angelica sinensis (Oliv) Diels 10 gram, Scrophularia ningpoensis Hemsl 15 gram, Ligusticum chuanxiong Hort 10 gram, Rheum palmatum L 6～10 gram, Cordycep sinensis 3 gram) to treat. Decoction of the medicine in water,2 times oral, every day. Two groups were treated for 08 weeks. Observed clinical effects and changes in clinical symptom score, fasting blood glucose (FBG) testing before and after treatment, renal function (BUN, Cr), lipids (Chol, TG),24-hour urine protein, serum TNFα, IL-6, hs-CRP of change.
Results:
1.The symptom scores after treatment compared with before treatment significantly decreased, the difference was significant (P<0.01), showed that two groups can improve the clinical symptoms of DN. The study group improved more significantly in clinical symptom score, compared with the control group, the difference was statistically significant (P<0.01).
2. After treatment, renal function indexes BUN, Cr were improved, compared with before treatment, the difference was significant (P<0.05); in comparison with the control group after treatment, the difference was significant (P<0.05)
3. After treatment, FBG decreased significantly, compared with before treatment, the differences were highly significant (P<0.01); after treatment between the two groups, the difference was not statistically significant (P> 0.05), suggest two glucose observation throughout the treatment are control within the specified scope. After treatment, the 24h urinary protein decreased in varying degrees, compared with before treatment, the difference was significant or very significant (P<0.05, P<0.01); the study group decreased significantly better than the control group, the difference was significant (P<0.05).
4. After treatment, TC, TG values decreased in varying degrees, compared with before treatment, the difference was significant or very significant (P<0.05, P<0.01); and the study group decreased more significantly than the control group The difference was significant (P<0.05).
5. After treatment, Hs-CRP values were significantly decreased compared with before treatment, the differences were highly significant (P<0.01); and the study group than the control group decreased obviously out, the difference was significant (P<0.01). Study group, IL-6, TNF-αwere significantly reduced after treatment, compared with before treatment, the difference was significant (P<0.05); compared with the control group after treatment, differences were also significant (P<0.05). Control group, although the index decreased after treatment, but in comparison with the before the difference was not statistically significant (P> 0.05).
6. After 08 weeks of treatment, the study group,8 of 30 cases are markedly effective,18 of 30 cases are effective and 4 of 30 cases are not effective, total effective rate was 86.7% in the control group that 1 of 15 case is markedly effective,7 of 15cases are effective, 7 of 15 cases are not effective, total effective rate was 53.3%. The study group in comparison with controlled group the total effective rate, the difference was significant (P<0.05).
Conclusion:
1.Use of qi-tonifficating and yin-nourishing, blood stasis-removing and new regenerating the new Chinese herbal medicine (tangshenan) to treat DN patients after treatment the results showed that improving clinical symtoms and decreasing clinical symptom scores, reducing fasting 24-hour urine protein and improve kidney function, lipid metabolism
2. Diabetic nephropathy serum Hs-CRP, TNF-a, IL-6 levels increased abnormally, qi-tonifficating and yin-nourishing, blood stasis-removing and new regenerating, the new Chinese herbal medicine reduced significantly the lvel of inflammatory cytokines in patients such as Hs-CRP, TNF-a, IL-6 and improved the micro-inflammatory state DN
3. qi-tonifficating and yin-nourishing, blood stasis-removing and new regenerating, the new Chinese herbal medicine treated with good clinical efficacy of DN, through multi-link to delay DN progression of glomerular sclerosis, in which lower levels of inflammatory factors, inhibit or improve the inflammatory response may be the law anti-DN one of the mechanisms of glomerular sclerosis.
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