摘要
目的:观察补虚祛风方对5/6(A/I)大鼠残肾功能及肾脏纤维化的影响,并探讨其作用机制。方法:随机从35只SD雄性大鼠中取8只作为假手术组,其余27只制作5/6(A/I)慢性肾衰模型,2周后将18只造模成功的SD雄性大鼠,随机分为模型组、补虚祛风方组、科素亚组,每组6只;假手术组和模型组给予0.9%氯化钠溶液,治疗组分别给予相应的药物,干预8周后,检测各组大鼠肾功能:血肌酐(Scr)、尿素氮(BUN)、尿总蛋白/肌酐(PCR);苏木精-伊红(HE)染色、过碘酸雪夫(PAS)染色、Masson染色观察肾组织病理变化;蛋白免疫印迹法检测肾纤维化相关蛋白:纤维连接蛋白(FN)、α-平滑肌肌动蛋白(α-SMA)、增殖细胞核抗原(PCNA);炎症因子白介素-6(IL-6)、白介素-1β(IL-1β)及缺氧诱导因子-1α(HIF-1α)蛋白表达水平;免疫组化法检测HIF-1α、肿瘤坏死因子-α(TNF-α)的表达。结果:与假手术组比较,模型组的BUN、Scr、PCR均升高;残余肾组织的肾小球结构紊乱,球囊粘连,肾小管管腔扩张,肾小球、肾小管周围纤维化,肾间质大量胶原蛋白沉积及炎性细胞浸润,肾组织中FN、α-SMA、PCNA、IL-6、IL-1β、HIF-1α、TNF-α蛋白表达均明显升高。与模型组比较,补虚祛风方组和科素亚组的BUN、Scr、PCR均下降;残余肾组织的肾小球结构紊乱和肾小管扩张、炎性细胞浸润及肾纤维化均改善;肾组织中FN、α-SMA、PCNA、IL-6、IL-1β、HIF-1α、TNF-α蛋白表达均明显下降。结论:补虚祛风方可以有效保护肾功能,改善肾脏病理损害,其机制可能为通过改善缺氧,下调炎症因子表达,进而发挥抗纤维化的作用。
Objective:To observe the effect of Buxu Qufeng prescription on renal interstitial fibrosis in 5/6(A/I)rats and explore its mechanism.Methods:Eight SD male rats were randomly selected from 35 SD male rats as the sham-operated group.The remaining 27 rats underwent surgery to establish a 5/6(A/I)a chronic renal failure model model.After 2 weeks,18 SD male rats with successful model induction were randomly divided into three groups(6 rats per group):the model group,the Buxu Qufeng prescription group(a traditional Chinese herbal formula),and the Cozaar group(losartan potassium tablets).Saline was given to the sham-operated group and the model group,and the corresponding drugs were given to the treatment group respectively.After 8 weeks of administration,the renal functions of rats in each group were measured:serum creatinine(Scr),blood urea nitrogen(BUN),urine protein-to-creatinine ratio(PCR).The renal histopathological changes were observed by HE,PAS,and Masson staining.Western blot was used to detect proteins related to renal interstitial fibrosis:fibronectin(FN),α-smooth muscle actin(α-SMA),proliferating cell nuclear antigen(PCNA);proinflammatory cytokine interleukin-6(IL-6),interleukin-1β(IL-1β)and Hypoxia-inducible factor-1α(HIF-1α);The expression of HIF-1αand tumor necrosis factor-α(TNF-α)was detected using immunohistochemistry.Results:compared with the sham-operated group,BUN,Scr,and PCR were elevated in the model group;the glomerular structure of the residual renal tissues was disorganized,with adhesion of the balloon,dilatation of the tubular lumen of the renal tubes,glomerulo-tubular and peri-tubular fibrosis,and a large amount of collagen deposition and inflammatory cell infiltration in the interstitium of the kidneys.The renal tissues were infiltrated with FN,α-SMA,PCNA,and IL-6,IL-1β,HIF-1α,TNF-α protein expression were significantly elevated in renal tissue.Compared with the model group,BUN,Scr and PCR decreased in the Buxu Qufeng prescription group and the Cozaar group.The glomerular structural disorder and tubular dilatation,inflammatory cell infiltration and renal interstitial fibrosis of the residual renal tissues improved.And the protein expression of FN,α-SMA,PCNA,IL-6,IL-1β,HIF-1α and TNF-α in the renal tissue was significantly decreased.Conclusion:Buxu Qufeng prescription can effectively protect renal function and improve renal pathological damage,and its mechanism may be related to improve hypoxia,down-regulate the expression of proinflammatory cytokine,and then play an anti-fibrotic role.
作者
岳靓
米秀华
杨柳易
YUE Liang;MI Xiuhua;YANG Liuyi(Baoshan Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201999,China)
出处
《陕西中医》
2025年第9期1160-1165,1177,共7页
Shaanxi Journal of Traditional Chinese Medicine
基金
国家自然科学基金资助项目(82205018)
上海市糖尿病肾病中医专病联盟建设项目[ZY(2021-2023)-0302]
上海市宝山医院优秀青年医学人才培养项目(2022BY006)
米秀华宝山区名中医传承工作室项目(BSMZYGZS-202409)。
关键词
慢性肾脏病
补虚祛风方
肾纤维化
缺氧
炎症
缺氧诱导因子-1Α
Chronic kidney disease
Buxu Qufeng prescription
Renal interstitial fibrosis
Hypoxia
Inflammation
Hypoxia-inducible factor-1α
