管周毛细血管密度下降致低氧对慢性马兜铃酸肾病肾间质纤维化的影响

Influence of Hypoxia Caused by Decrease of Peritubular Capillary Density on Renal Interstitial Fibrosis of Chronic Aristolochic Acid Nephropathy

目的研究慢性马兜铃酸肾病(CAAN)管周毛细血管(PTC)密度下降致低氧对慢性马兜铃酸肾病肾间质纤维化进展的影响。方法将60只大鼠随机分为两组,CAAN组(n=30):给予关木通水煎剂灌胃8周;正常对照组(n=30)大鼠予饮用水灌胃8周。在第8、12、16周两组分别处死10只大鼠留取肾组织作病理、免疫组织化学染色和RT-PCR等检查。结果CAAN组不同时间点、不同组别低氧诱导因子-1α(HIF-1α)、结缔组织生长因子(CTGF)、金属蛋白酶组织抑制物-1(TIMP-1)、胶原-Ⅰ(Col-Ⅰ)和CD34表达间差异均有统计学意义(P<0·05);肾脏病理提示肾小管-间质损伤随时间呈进行性加重。PTC密度与HIF-1α、CTGF、TIMP-1、Col-I及相应mRNA的表达呈负相关。HIF-1α表达与CTGF、TIMP-1、Col-I及相应mRNA的表达呈正相关。结论CAAN肾脏PTC密度下降导致低氧与CAAN肾间质纤维化进展密切相关。

Objective To investigate the influence of hypoxia due to the decrease of density of peritubular capillary （PTC） on renal interstitial fibrosis of chronic aristolochic acid nephropathy （CAAN）. Methods Sixty Wistar rats were randomly divided into 2 groups： a CAAN group （n =30） and a control group （n =30）. The control group were given drinkingwater intragastric administration for 8 weeks. The CAAN group were administered intragastrically with decoction of caulis aristolochiae manshuriensis for 8 weeks. In the 8th, 12th and 16th weeks, we killed respectively ten rats from both groups, from which specimens of kidney tissue were collected to detect the expression of CD34, hypoxia - inducible factor -1α （ HIF -1α）, connective tissue growth factor （CTGF） , tissue inhibitor of matrix metalloproteinase - 1 （ TIMP - 1 ） and collagen -Ⅰ （ Col -Ⅰ） by pathlogy of kidney, immunohistochemistry and RT - PCR. Related analysis was conducted to study the relationship between these indices. Results CD34 expression and the density of PTC of the CAAN group were remarkably lower than those of the control group after 8 weeks. During the period of the 8th to the 16th week, CD34 expression and the density of PTC increased greatly, but a descendent tendency appeared in the CAAN group. The expression of HIF -1α, CTGF, TIMP - 1 and Col -Ⅰ also showed a ascendant tendency in the CAAN group after 8 weeks. Pathological changes of kidney appeared with an increase tendency. The density of PTC was correlated negatively with the expression of HIF -1α, CTGF, TIMP - 1 and Col -Ⅰ, and the expression of HIF -1α was correlated positively with that of HIF -1α, CTGF, TIMP - 1 and Col -Ⅰ in the CAAN group. Conclusion The decrease of the density of PTC was closely correlated with the development of renal interstitial fibrosis in CAAN.