子宫内膜异位症(EMS)是一种复发性和雌激素依赖性疾病。对于子宫内膜异位症,如深部子宫内膜异位症和卵巢子宫内膜样囊肿,手术是最有效的治疗方法。长期随访显示,手术治疗后子宫内膜异位症复发率高,所以术后需要药物来减少复发,促性腺激素释放激素激动剂(GnRH-a)是最常用的术后治疗药物.GnRH-a可以通过降低体内激素水平来减少治疗后子宫内膜异位症的复发。然而,使用GnRH-a可引起围绝经期症状,尤其是骨质疏松,骨丢失,和骨头疼痛,因此,GnRH-a的使用通常受到限制。补充疗法通常用于减轻由GnRH-a引起的不利影响。然而,长期使用激素类药物可能导致EMS复发,血栓形成,和乳腺癌。因此,迫切需要一种更安全,更有效的药物来减轻GnRH-a引起的不良反应。近年来,国内外学者研究发现,大头胡麻异丙醇提取物(ICR),作为植物提取物,能更好的缓解围绝经期妇女的症状。同时,一些研究初步证实,黑升麻制剂可以缓解EMS患者GnRH-a治疗引起的围绝经期症状。
探讨黑升麻制剂对GnRH-a诱导围绝经期症状大鼠模型骨代谢的影响。
通过注射GnRH-a建立围绝经期症状大鼠模型。以生理盐水(NS注射液)作为对照。根据建模方法和药物干预,将大鼠随机分为4组:GnRH-a注射液+生理盐水干预组(GnRH-a+NS),生理盐水注射对照组+生理盐水干预组(NS+NS),GnRH-a注射+雌二醇干预组(GnRH-a+E2),GnRH-a打针+黑升麻制剂干预组(GnRH-a+ICR)。用阴道涂片法鉴定大鼠模型,然后给予相应的药物干预28天。干预之后,大鼠被处死。通过双能X射线骨密度扫描仪检测大鼠股骨远端骨矿物质密度(BMD)。将大鼠胫骨骨组织脱钙并制成切片。HE染色观察各组大鼠胫骨的病理形态学变化。各组大鼠胫骨骨的组织形态计量学参数,如小梁骨体积(TBV),小梁厚度(TbTh),骨小梁数(TbN),和小梁间距(TbSp),通过使用自动图像分析系统进行检测和分析。
(1)GnRH-a+NS组股骨远端BMD水平明显低于NS+NS组,GnRH-a+E2和GnRH-a+ICR组(P<0.01),GnRH-a+E2和GnRH-a+ICR组的BMD水平略低于NS+NS组,但三组间差异无统计学意义(P>0.05)。(2)不同组胫骨在显微镜下的病理变化如下:NS+NS组胫骨骨小梁结构正常,没有小梁变薄或骨折,足弓结构正常.在GnRH-a+NS组中,一些小梁结构逐渐变细,拱形结构消失了,但小梁未见明显骨折。在GnRH-a+E2和GnRH-a+ICR组中,骨小梁结构正常,没有骨小梁变薄或骨折,足弓结构正常.(3)GnRH-a+INS组TBV水平明显低于NS+NS组,GnRH-a+E2和GnRH-a+ICR组(P<0.01,P<0.05,P<0.01),虽然NS+NS之间没有显著差异,GnRH-a+E2和GnRH-a+ICR组(P>0.05)。(4)四组间TbTh水平差异无统计学意义(P>0.05)。与NS+NS组相比,GnRH-a+NS中的TbTh水平,GnRH-a+E2和GnRH-a+ICR组呈下降趋势,而GnRH-a+E2和GnRH-a+ICR组的TbTh水平略高于GnRH-a+NS组。然而,差异无统计学意义(P>0.05)。(5)与NS+NS组相比,GnRH-a+NS中的TbN水平,GnRH-a+E2、GnRH-a+ICR组显著降低(P<0.05)。与GnRH-a+NS组相比,GnRH-a+E2和GnRH-a+ICR组TbN水平呈轻度下降趋势,但差异无统计学意义(P>0.05)。(6)GnRH-a+NS组TbSp水平明显高于NS+NS组,GnRH-a+E2和GnRH-a+ICR组(P<0.01),虽然NS+NS之间没有显著差异,GnRH-a+E2和GnRH-a+ICR组(P>0.05)。
注射GnRH-a可以达到预期的效果。注射GnRH-a可能导致大鼠骨量丢失。黑色升麻准备,比如雌激素,可能对注射GnRH-a引起的骨量减少有保护作用。
Endometriosis (EMS) is a relapsing and estrogen-dependent disease. For endometriosis such as deep endometriosis and ovarian endometrioid cysts, surgery is the most effective treatment. Long-term follow-up showed that the recurrence rate of endometriosis after surgical treatment was high, so postoperative drugs were needed to reduce recurrence, and Gonadotropin-releasing hormone agonists (GnRH-a) were the most commonly used drug for postoperative management.GnRH-a may reduce the post-treatment endometriosis relapses by lowering the hormone levels in the body. However, the use of GnRH-a can give rise to perimenopausal symptoms, especially osteoporosis, bone loss, and bone pain, for which reason GnRH-a use is often limited. The add-back therapy is often used to alleviate the untoward effects caused by GnRH-a. However, long-term use of hormone drugs may lead to EMS recurrence, thrombosis, and breast cancer. Therefore, a safer and more effective drug is urgently needed to alleviate the untoward effects caused by GnRH-a. In recent years, scholars at home and abroad have found that isopropanolic
Cimicifuga racemosa extract (ICR), as a plant extract, can better relieve the symptoms of perimenopausal women. At the same time, some studies have initially confirmed that black cohosh preparations can relieve the perimenopausal symptoms caused by GnRH-a treatment in EMS patients.
To investigate the effect of black cohosh preparations on the bone metabolism of rat models with GnRH-a-induced perimenopausal symptoms.
The rat models of perimenopausal symptoms were established by GnRH-a injection. and normal saline (NS injection) was used as the control. According to the modeling method and drug intervention, the rats were randomly divided into four groups: GnRH-a injection + saline intervention group (GnRH-a + NS), saline injection control + saline intervention group (NS + NS), GnRH-a injection + estradiol intervention group (GnRH-a + E2), and GnRH-a injection + black cohosh preparation intervention group (GnRH-a + ICR). The rat models were identified with the vaginal smear method, and then the corresponding drug intervention was administrated for 28 days. After the intervention, the rats were sacrificed. The rats\' bone mineral density (BMD) of the distal femur was detected by a dual-energy X-ray bone density scanner. Rat tibia bone tissues were decalcified and made into slices. The pathological and morphological changes of rat tibial bones in each group were observed through HE staining. Histomorphometry parameters of rat tibial bones in each group, such as trabecular bone volume (TBV), trabecular thickness (TbTh), trabecular number (TbN), and trabecular spacing (TbSp), were detected and analyzed by using an automatic image analysis system.
(1) The BMD level of the distal femur in the GnRH-a + NS group was significantly lower than the NS + NS, GnRH-a + E2, and GnRH-a + ICR groups (P<0.01), the BMD levels in GnRH-a + E2 and GnRH-a + ICR groups were slightly lower than the NS + NS group, but there was no significant difference among the three groups (P>0.05). (2) The pathological changes of the tibia bones under the microscope in different groups were as follows: The tibia bone trabecular structure was normal in the NS + NS group, without trabecular thinning or fracture, and the arch structure was normal. In the GnRH-a + NS group, some trabecular structures tapered, the arch structure disappeared, but no obvious bone fracture was observed in the trabecula. In the GnRH-a + E2 and GnRH-a + ICR groups, the trabecular structures were normal, without trabecular bone thinning or fracture, and the arch structures were normal. (3) The TBV level of the GnRH-a + INS group was significantly lower than that of the NS + NS, GnRH-a + E2 and GnRH-a + ICR groups (P<0.01, P<0.05, P<0.01), while there was no significant difference among NS + NS, GnRH-a + E2 and GnRH-a + ICR groups (P>0.05). (4) The TbTh levels in the four groups had no significant difference (P>0.05). Compared with the NS + NS group, the TbTh levels in the GnRH-a + NS, GnRH-a + E2, and GnRH-a + ICR groups showed a descending tendency, while the TbTh levels in the GnRH-a + E2 and GnRH-a + ICR groups were slightly higher than that of the GnRH-a + NS group. However, such differences were not significant statistically (P>0.05). (5) Compared with the NS + NS group, the TbN levels in the GnRH-a + NS, GnRH-a + E2, and GnRH-a + ICR groups decreased remarkably (P<0.05). Compared with the GnRH-a + NS group, the TbN levels in the GnRH-a + E2 and GnRH-a + ICR groups showed a mild descending tendency, but such differences were not significant statistically (P>0.05). (6) The TbSp level of the GnRH-a + NS group was significantly higher than that of the NS + NS, GnRH-a + E2, and GnRH-a + ICR groups (P<0.01), while there was no significant difference among NS + NS, GnRH-a + E2 and GnRH-a + ICR groups (P>0.05).
The GnRH-a injection could achieve the desired effect. GnRH-a injection may lead to the loss of bone mass in rats. Black cohosh preparations, like estrogen, may have a protective effect on bone mass loss caused by GnRH-a injection.