温肾固疏方对去势大鼠骨组织中Ⅰ型胶原及组织蛋白酶 K 表达的影响

目的 研究温肾固疏方对绝经后骨质疏松症的防治作用。方法 通过切除大鼠双侧卵巢建立绝经后骨质疏松大鼠模型。造模后，SD大鼠随机分为模型组、雌激素组、温肾固疏方高、中、低剂量组，每组8只。假手术组仅切除卵巢旁脂肪组织。干预2个月后,通过HE染色观察骨组织、肾组织形态；ELISA法测定血清PICP、ICTP、CTX、NTX的含量；免疫组化法测定Col I、Cath K表达率的变化。结果 与假手术组比较，模型组大鼠血清ICTP、NTX、CTX含量均明显升高（P＜0.01），骨组织形态改变与骨质疏松症一致，肾组织出现炎性改变，骨组织中Cath K含量明显增高（P＜0.01），Col I蛋白含量显著降低（P＜0.01）;与模型组相比，血清ICTP、NTX、CTX含量显著降低（P＜0.05），且温肾固疏方高剂量组比中、低剂量组表达明显。温肾固疏方中、高剂量组血清PICP含量显著增高（P＜0.01）。各治疗组骨组织形态改善，肾组织炎性改变减轻。各治疗组骨组织Cath K蛋白的表达均降低（P＜0.01），Col I蛋白表达显著升高（P＜0.01）。结论 温肾固疏方能够通过下调破骨细胞Cath K的表达来抑制骨基质中Col I的分解，起到治疗绝经后骨质疏松症的作用。

Effects of the warming kidney and astringing formula on type I collagen (Col I) metabolism and the expression of Cathepsin K in bone tissue of ovariectomized rats

Objective To study the preventive and therapeutic effect of the warming kidney and astringing formula on postmenopausal osteoporosis. Methods Postmenopausal osteoporosis model was established in SD rats using ovariectomy (OVX). After successful modeling, 40 rats were randomly divided into model group, estradiol valerate group, and high-, middle-, and low-dose warming kidney and astringing formula groups. Rats in the sham group were resected of adipose tissue only. After treatment for 2 months, bone tissue and kidney tissue morphology was observed using HE staining; the content of PICP, ICTP, CTX and NTX were determined by ELISA. The expression of type I collagen (Col I) and cathepsin K (Cath K) in bone tissue was determined by immunohistochemistry. Results Compared with those in sham group, serum ICTP, NTX and CTX were all significantly increased (P<0.01) in the model group. The histomorphological change of the bone in the model group was consistent with osteoporosis, and the kidney tissue has undergone inflammatory changes; the expression of Cath K in bone tissue was increased (P<0.01), and the expression of Col I protein was significantly decreased (P<0.01). Compared with the model group, the levels of serum ICTP, NTX and CTX were significantly decreased (P<0.05), and the decrease in the high dose warming kidney and astringing formula group was significantly greater than that in the medium and low dose groups. The serum PICP content in the middle and high dose groups of warming kidney and astringing formula was significantly increased (P<0.01). Bone tissue morphology was improved in each treatment group, and the inflammatory changes in the renal tissue were alleviated. The expression of Cath K was decreased in all treatment groups (P<0.01), and the expression of Col I protein was significantly increased (P<0.01). Conclusion The expression of Cath K of osteoclasts can be reduced by the warming kidney and astringing formula, which can inhibit the decomposition of Col I in bone matrix and play certain role in the treatment of postmenopausal osteoporosis.