Rosenberg M E, Manivel J C, Carone F A, Kanwar Y S
Department of Medicine, University of Minnesota, Minneapolis 55455, USA.
J Am Soc Nephrol. 1995 Mar;5(9):1669-74. doi: 10.1681/ASN.V591669.
Phenol II is a cystogenic chemical that rapidly induces renal cysts, which regress after drug withdrawal. Cyst formation in this model parallels changes in the tubular basement membrane. Clusterin is a potent cohesive factor induced in states of tissue remodeling. The purpose of this study was to determine if renal clusterin was increased in the Phenol II model and to define the time course and distribution of its induction. Male Sprague-Dawley rats were given, by daily gavage, Phenol II (1.2 mg/kg per day) or vehicle (control). The kidneys were harvested after 1, 2, or 4 days of Phenol II treatment or 3 or 7 days after drug withdrawal. An increase in immunoreactive clusterin was seen in the kidneys of Phenol II-treated rats but not in controls. The appearance of clusterin followed a time course similar to that for cyst formation, with expression confined to the epithelial lining and intratubular casts of dilated or cystic tubules. After Phenol II withdrawal, renal cysts regressed and clusterin staining disappeared. The development of cysts was associated with an increase in clusterin mRNA that decreased after drug withdrawal. In conclusion, a marked, yet reversible induction of clusterin occurred in chemically induced polycystic kidney disease. The function of clusterin in this setting remains enigmatic.
苯酚II是一种致囊肿化学物质，可迅速诱发肾囊肿，停药后囊肿会消退。该模型中的囊肿形成与肾小管基底膜的变化平行。聚集素是在组织重塑状态下诱导产生的一种强大的黏附因子。本研究的目的是确定在苯酚II模型中肾聚集素是否增加，并确定其诱导的时间进程和分布。将雄性Sprague-Dawley大鼠每日经口灌胃给予苯酚II（1.2毫克/千克/天）或赋形剂（对照）。在苯酚II治疗1、2或4天后或停药后3或7天采集肾脏。在苯酚II处理的大鼠肾脏中可见免疫反应性聚集素增加，而在对照组中未见增加。聚集素的出现时间进程与囊肿形成相似，其表达局限于扩张或囊性肾小管的上皮内衬和管内铸型。停药后，肾囊肿消退，聚集素染色消失。囊肿的发展与聚集素mRNA增加有关，停药后该mRNA减少。总之，在化学诱导的多囊肾病中发生了明显但可逆的聚集素诱导。在这种情况下，聚集素的功能仍然不明。
