1.Invasion and Metastasis in Colorectal Cancer Mediated by Traditional Chinese Medicine via Cell Signaling Pathway: A Review
Min GUO ; Wenyan YU ; Naicheng ZHU ; Yuwei YAN ; Chen ZHONG ; Xiudan CHEN ; Nanxin LI ; Guojuan WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):323-330
Colorectal cancer is a common and malignant tumor in the digestive tract. Invasion and metastasis of cancer cells are key factors leading to the high mortality rate and postoperative recurrence of colorectal cancer. Chemotherapy is the main treatment method for preventing recurrence of this disease. However, there are many toxic side effects in clinical application, which seriously hinder the treatment process. Therefore, it is imperative to search for efficient and low-toxicity drugs. Traditional Chinese medicine (TCM) has a long history of treating colorectal cancer and offers advantages such as safety, effectiveness, multiple targets, multiple pathways and minimal toxic side effects, which have made it increasingly popular worldwide. According to TCM, the pathogenesis of colorectal cancer is rooted in both deficiency and excess. TCM formulas mainly focus on tonifying the body to address the invasion and metastasis of colorectal cancer, such as Jianpi compound, Jianpi Xiaoai decoction, and Bushen Jiedu Sanjie decoction. TCM monomers, such as emodin, berberine, and tanshinone, mainly focus on clearing heat and removing toxin, circulating blood and transforming stasis, and resolving swelling and dispersing nodules. Signaling pathways play a crucial role for analyzing invasion and metastasis, and research has shown that pathways such as Wnt/β-catenin, phosphatidylinositol-3 kinase/protein kinase (PI3K/Akt), Janus kinase 2/signal transduction and transcription activating factor 3 (JAK2/STAT3), nuclear factors-κB (NF-κB), vascular endothelial growth factor (VEGF) play important roles in the invasion and metastasis of colorectal cancer. The invasion and metastasis of colorectal cancer can be inhibited via regulating the key proteins and related factors in these pathways. In this review, we searched various literature databases, such as PubMed, China National Knowledge Infrastructure (CNKI), and VIP, using keywords such as "colorectal cancer", "signaling pathway", "invasion and metastasis", and "traditional Chinese medicine", to summarize and analyze the relevant pathways of TCM compounds and monomers against invasion and metastasis of colorectal cancer published in the past five years. The review aims to provide new insights and references for in-depth research on the therapy for invasion and metastasis of colorectal cancer and new drug development.
2.Phenomics of traditional Chinese medicine 2.0: the integration with digital medicine
Min Xu ; Xinyi Shao ; Donggeng Guo ; Xiaojing Yan ; Lei Wang ; Tao Yang ; Hao LIANG ; Qinghua PENG ; Lingyu Linda Ye ; Haibo Cheng ; Dayue Darrel Duan
Digital Chinese Medicine 2025;8(3):282-299
Abstract
Modern western medicine typically focuses on treating specific symptoms or diseases, and traditional Chinese medicine (TCM) emphasizes the interconnections of the body’s various systems under external environment and takes a holistic approach to preventing and treating diseases. Phenomics was initially introduced to the field of TCM in 2008 as a new discipline that studies the laws of integrated and dynamic changes of human clinical phenomes under the scope of the theories and practices of TCM based on phenomics. While TCM Phenomics 1.0 has initially established a clinical phenomic system centered on Zhenghou (a TCM definition of clinical phenome), bottlenecks remain in data standardization, mechanistic interpretation, and precision intervention. Here, we systematically elaborates on the theoretical foundations, technical pathways, and future challenges of integrating digital medicine with TCM phenomics under the framework of “TCM phenomics 2.0”, which is supported by digital medicine technologies such as artificial intelligence, wearable devices, medical digital twins, and multi-omics integration. This framework aims to construct a closed-loop system of “Zhenghou–Phenome–Mechanism–Intervention” and to enable the digitization, standardization, and precision of disease diagnosis and treatment. The integration of digital medicine and TCM phenomics not only promotes the modernization and scientific transformation of TCM theory and practice but also offers new paradigms for precision medicine. In practice, digital tools facilitate multi-source clinical data acquisition and standardization, while AI and big data algorithms help reveal the correlations between clinical Zhenghou phenomes and molecular mechanisms, thereby improving scientific rigor in diagnosis, efficacy evaluation, and personalized intervention. Nevertheless, challenges persist, including data quality and standardization issues, shortage of interdisciplinary talents, and insufficiency of ethical and legal regulations. Future development requires establishing national data-sharing platforms, strengthening international collaboration, fostering interdisciplinary professionals, and improving ethical and legal frameworks. Ultimately, this approach seeks to build a new disease identification and classification system centered on phenomes and to achieve the inheritance, innovation, and modernization of TCM diagnostic and therapeutic patterns.
3.Mechanism of Shenshuai Xiezhuo Decoction in Intervention of Chronic Kidney Disease Combined with Atherosclerosis Based on Regulation of PI3K/Akt/mTOR Signaling Pathway by miRNA126
Gengxin LIU ; Gedi ZHANG ; Wenqi YUAN ; Fusheng LI ; Min GUO ; Fuli LUO ; Ziyou YAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(9):48-55
ObjectiveExploring the role of microRNA126 (miRNA126) in chronic kidney disease combined with atherosclerosis (CKD AS) by regulating the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway and the mechanism of Shenshuai Xiezhuo decoction in the intervention of CKD AS rats with 5/6 nephrectomy combined with high-fat feeding. MethodA total of 60 SD rats were randomly divided into sham operation group, model group, losartan group, and low, medium, and high dose groups of Shenshuai Xiezhuo decoction. The CKD AS rat model was established by 5/6 nephrectomy combined with high-fat feeding for 10 weeks. The low, medium, and high dose groups (6.0, 12.0, 24.0 g·kg-1·d-1) of Shenshuai Xiezhuo decoction and the losartan group (20 mg·kg-1·d-1) were gavaged, and the corresponding intervention was carried out for eight weeks. Then, the rats were killed, and samples were collected for corresponding detection. Fully automated biochemical analyzers were used to detect kidney function and blood lipids in rats: blood creatinine (SCr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels. Hematoxylin-eosin (HE) and Masson staining of aortic tissue and pathological observation under a light microscope were carried out, and autophagosomes and autophagy lysosomes were observed by transmission electron microscopy. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to determine the mRNA levels of miRNA126, PI3K, Akt, and mTOR in rats, and Western blot was used to determine the protein expression levels of phosphorylated (p)-PI3K, PI3K, p-Akt, Akt, p -mTOR, mTOR, benzyl chloride 1 (Beclin-1), and microtubule-associated protein light chain 3Ⅱ/Ⅰ (LC3Ⅱ/LC3Ⅰ). ResultCompared with the sham operation group, the serum SCr, BUN, TC, TG, and LDL-C in the model group were significantly increased (P<0.01). Compared with the model group, the SCr, BUN, TC, TG, and LDL-C were decreased in the losartan group and low, medium, and high dose groups of Shenshuai Xiezhuo decoction (P<0.05). Compared with the sham operation group, thickening plaques, infiltration of mononuclear macrophages, a small number of foam cells, disordered arrangement of smooth muscle fibers in the tunica media, and increased collagen fibers were observed in the model group, and the lesions in the losartan group and Shenshuai Xiezhuo decoction groups were alleviated compared with those in the model group. Compared with the model group, the number of autophagosomes and autophagy lysosomes increased in the medium and high dose groups of Shenshuai Xiezhuo decoction. Compared with the sham operation group, the expression of miRNA126 in the aortic tissue of the model group was significantly decreased (P<0.01), and the mRNA expressions of PI3K, Akt, and mTOR were significantly increased (P<0.01). Compared with the model group, the expression of miRNA126 in the aortic tissue of rats in high, medium, and low dose groups of Shenshuai Xiezhuo decoction and losartan group was significantly increased (P<0.01), while the mRNA expressions of PI3K, Akt, and mTOR were significantly decreased (P<0.01). Compared with the sham operation group, the protein expressions of p-PI3K, PI3K, p-Akt, Akt, p-mTOR, and mTOR in the model group were significantly increased (P<0.01), while the protein levels of Beclin-1, LC3Ⅰ, and LC3Ⅱ were significantly decreased (P<0.01). Compared with the model group, the protein expressions of p-PI3K, PI3K, p-Akt, Akt, p-mTOR, and mTOR in the losartan group and low, medium, and high dose groups of Shenshuai Xiezhuo decoction were decreased (P<0.05), while the protein levels of Beclin-1 and LC3Ⅱ/LC3Ⅰ were increased (P<0.05). ConclusionThe expression of miRNA126 is decreased in the aortic tissue of CKD AS rats, and the PI3K/Akt/mTOR pathway is activated to inhibit autophagy flux. Shenshuai Xiezhuo decoction regulates the PI3K/Akt/mTOR signaling pathway through miRNA126, restores the autophagy of aortic endothelial cells, protects the damage of CKD vessels, reduces the formation of As plaques, and slows the development of cardiovascular complications.
4.Regulatory Mechanism of Drug-Containing Serum of Jinghou Zengzhi Prescription on GDF9 Expression and Apoptosis of Ovarian Granulosa Cells in Rats with Controlled Ovarian Hyperstimulation
Zhen YANG ; Xiao-Yan CHEN ; Shao-Ru JIANG ; Shu-Zhu YE ; Xiao-Hong FANG ; Wei-Min DENG ; Xin-Yu GUO
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(3):735-741
Objective To observe the regulatory mechanism of drug-containing serum of Jinghou Zengzhi Prescription based on qi and blood replenishing method on the expression of growth and differentiation factor 9(GDF9)and apoptosis of ovarian granulosa cells in rats with controlled ovarian hyperstimulation(COH).Methods Serum of COH rats(blank serum)and serum of COH rats gavaged by the Jinghou Zengzhi Prescription were prepared.A COH rat model was established and ovarian granulosa cells were collected.The experiment was divided into 5 groups:blank serum group,drug-containing serum group,drug-containing serum+SB203580[p38 mitogen-activated protein kinase(p38MAPK)inhibitor]group,drug-containing serum + PDTC[nuclear transcription factor κB(NF-κB)inhibitor]group,drug-containing serum + SB203580 + PDTC group.The mRNA expression levels of p38MAPK,casein kinase 2(CK2),nuclear transcription factor κB inhibitor α(IκBα),NF-κB and GDF9 were detected by real-time quantitative polymerase chain reaction(qRT-PCR),and GDF9 protein expression level was detected by Western Blot,and ovarian granulosa cell apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL).Results The drug-containing serum of Jinghou Zengzhi Prescription decreased the mRNA expressions of p38MAPK and NF-κB,elevated the mRNA expressions of CK2 and IκBα,increased the mRNA and protein expression levels of GDF9,and decreased the apoptosis rate of ovarian granulosa cells in COH rats.The addition of p38MAPK inhibitor SB203580 alone and the addition of NF-κB inhibitor PDTC alone both promoted the mRNA and protein expressions of GDF9 and reduced the apoptosis rate of granulosa cells.Conclusion The drug-containing serum of Jinghou Zengzhi Prescription based on qi and blood replenishing method can promote the expression of GDF9 and inhibit the apoptosis of ovarian granulosa cells in rats with COH,and its mechanism may be related to the regulation of the expression of genes of the dual signaling pathways of p38MAPK and NF-κB.
5.The value of high-throughput sequencing data reanalysis in identifying ERBB2 amplification in colorectal cancer patients
Min-Na SHEN ; Li ZHANG ; Xin-Ning CHEN ; Fei HUANG ; Chao-Gang BAI ; Li-Meng CHEN ; Hai-Xiang PENG ; Yan ZHOU ; Bei-Li WANG ; Bai-Shen PAN ; Wei GUO
Fudan University Journal of Medical Sciences 2024;51(2):166-171
Objective To evaluate the value of high-throughput sequencing(HTS)data reanalysis that does not include ERBB2 copy number variation(CNV)analysis,in identifying ERBB2 amplification in patients with colorectal cancer.Methods The HTS data of 252 cases of colorectal cancer diagnosed by pathological biopsy who received peripheral blood cfDNA HTS detection samples were retrospectively analyzed.According to the HTS data of ERBB2 non-amplified samples judged by immunohistochemistry(IHC)and/or fluorescence in situ hybridization(FISH),the number of chromosome 17(Chr17)reads in the total number of reads was calculated the range of the ratio was initially determined as the threshold for prompting ERBB2 amplification.Suspected positive samples were screened according to thresholds and verified by digital PCR,IHC and FISH.Results The proportion of the number of Chr17 reads accounts for the number of total reads in the 89 cases of ERBB2 non-amplified samples determined by IHC and/or FISH ranged from 0.188 to 0.299(0.239±0.192).Using 0.298(1.25 times the mean)as the threshold indicating ERBB2 amplification,the data of 163 samples were analyzed,of which 7 cases were suspected to be positive,and the ratio ranged from 0.302 to 0.853.Among them,5 cases were determined to be positive by IHC and/or FISH,and 6 cases were confirmed to be positive by digital PCR.The ratio of the number of Chr17 reads to the number of total reads was positively correlated with the ratio of ERBB2/EIF2C1,and the correlation was good(r2=0.909).Conclusion The high-throughput sequencing data that does not cover the ERBB2 CNV analysis has a certain hint value for ERBB2 amplification in patients with colorectal cancer.
6.Effect of timely induction intervention on postpartum urination of primipara in vaginal delivery
Dan GUO ; Min LING ; Zijing WANG ; Yan BI ; Huijing SHI ; Xiaoyan LIU ; Fenghui CONG
Chinese Journal of Practical Nursing 2024;40(6):401-406
Objective:To explore the effect of timely induction intervention on postpartum urination in primipara during vaginal delivery, so as to provide the evidence for preventing the occurrence of postpartum urinary retention and relieving the pain of primipara.Methods:This study adopted a randomized controlled trial design, and selected 400 cases of primipara who were hospitalized for vaginal delivery in the Obstetric Department of Dalian Women and Children's Medical Group Sports New Town Hospital from June 2021 to September 2022 as the study objects by convenience sampling method. They were divided into the intervention group and the control group with 200 cases each by random number table method, and the control group received routine postpartum care. Instruct active urination within 6 hours after delivery. The intervention received timely induction urination intervention. The general condition and bladder urine volume of the women in the intervention group were evaluated at 2, 4, 6 h after delivery, respectively, and personalized guidance was implemented, including the frequency of massage of the bottom of the uterus, the control of water intake, the selection of methods and timing of inducing urination, etc., and routine postpartum care was given when the women completed their first urination and had no complaints of discomfort. The first urination time, first urination volume, first bladder irritation during the first urination and the incidence of postpartum urinary retention in different periods were compared between the two groups.Results:The patients in the control group were (29.60 ± 3.20) years old, while the patients in the intervention group were (28.81 ± 3.42) years old. The first urination time in the intervention group was (6.89 ± 2.18) h, which was shorter than that in the control group (9.11 ± 3.86) h, and the difference was statistically significant ( t=-2.49, P<0.01). The first urination volume in the intervention group was (322.36 ± 120.15) ml, which was higher than that in the control group (262.93 ± 105.68) ml, and the difference was statistically significant ( t=3.39, P<0.05). The incidence of the first bladder irritation in the intervention group was 22.0%(44/200), which was lower than that in the control group 33.5%(67/200), and the difference was statistically significant ( χ2=6.60, P<0.05). The incidence of postpartum urinary retention within 24 h in the intervention group was 5.5%(11/200), which was lower than that in the control group 11.5%(23/200), and the difference was statistically significant ( χ2=4.63, P<0.05). The incidence of postpartum urinary retention within 1 week in the intervention group was 9.5%(19/200), which was lower than that in the control group 16.5%(33/200), and the difference was statistically significant ( χ2=4.33, P<0.05). There was no significant difference in the incidence of postpartum urinary retention within 24 to 72 h between the two groups ( P>0.05). Conclusions:Timely induction intervention can reduce the incidence of postpartum urinary retention, shorten the time of first urination, increase the volume of first urination and improve the comfort of first urination, which is worthy of clinical application.
7.Clinical trial of Morinda officinalis oligosaccharides in the continuation treatment of adults with mild and moderate depression
Shu-Zhe ZHOU ; Zu-Cheng HAN ; Xiu-Zhen WANG ; Yan-Qing CHEN ; Ya-Ling HU ; Xue-Qin YU ; Bin-Hong WANG ; Guo-Zhen FAN ; Hong SANG ; Ying HAI ; Zhi-Jie JIA ; Zhan-Min WANG ; Yan WEI ; Jian-Guo ZHU ; Xue-Qin SONG ; Zhi-Dong LIU ; Li KUANG ; Hong-Ming WANG ; Feng TIAN ; Yu-Xin LI ; Ling ZHANG ; Hai LIN ; Bin WU ; Chao-Ying WANG ; Chang LIU ; Jia-Fan SUN ; Shao-Xiao YAN ; Jun LIU ; Shou-Fu XIE ; Mao-Sheng FANG ; Wei-Feng MI ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(6):815-819
Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P<0.05).After continuation treatment,the remission rate was 54.59%(202 cases/370 cases),and the recurrence rate was 6.49%(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35%(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.
8.A multi-dimensional analysis of pollen broadcasting concerns in Chinese population: a large-scale multi-center cross-sectional survey
Chiyu XU ; Yanshu ZHANG ; Ning LUAN ; Xiangyi LIU ; Dayang QIN ; Hongmin WANG ; Xuping XIAO ; Shuihong ZHOU ; Jie ZHANG ; Ping ZHANG ; Yuqing BAI ; Pengpeng WANG ; Yan QI ; Zhongwu SUN ; Zhuang LIU ; Luo BA ; Wenchao WANG ; Xing LU ; Min WANG ; Rui GUO ; Deyi SUN ; Liyuan TAO ; Li ZHU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(1):2-11
Objective:To investigate the concern about pollen broadcasting in Chinese population from multiple dimensions and to understand the information about allergic rhinitis (AR) in China by analyzing related factors.Methods:From March 1 to September 30, 2022, a large-scale multi-center cross-sectional survey was conducted based on the Questionnaire Star platform in 21 Chinese hospitals. A total of 7 056 subjects from 7 regions in China: Northeast, North, East, Central, South, Southwest, and Northwest China were included. Basic characteristics (including social demographic characteristics and disease characteristics of AR patients), concern about pollen broadcasting, the willingness of pollen-induced AR (PiAR) patients to receive pollen broadcasting, and the treatment satisfaction rate of AR patients were collected. The chi-square test, multivariate linear regression model, and Logistic regression analysis were used to analyze the concern about pollen broadcasting in the Chinese population and related factors from multiple dimensions.Results:Among 7 056 subjects, 23.02% were concerned about pollen broadcasting. Among 3 176 self-reported AR and 1 019 PiAR patients, 25.60% and 39.16% were concerned about pollen broadcasting, respectively, which was higher than that of non-AR or non-PiAR subjects ( χ2 value was 21.74 and 175.11, respectively, both P<0.001). Among AR patients, the proportion of spring and autumn allergen-positive patients concerned about pollen broadcasting was higher than that in perennial allergen-positive patients ( χ2 value was 20.90 and 19.51, respectively, both P<0.001). The proportion of AR patients with asthma, sinusitis, allergic conjunctivitis, and cardiovascular and cerebrovascular diseases was higher than those without complications ( χ2 value was 50.83, 21.97, 56.78, 7.62, respectively, all P<0.05). The proportion of AR patients in North China who could find pollen broadcasting locally was 31.01%, significantly higher than those in other regions (all P<0.05). Multivariate linear regression model analysis showed that among PiAR patients, those with higher per capita household income and higher AR disease cognition levels had been concerned about pollen broadcasting in the past, and those complicated with allergic conjunctivitis had stronger intention to receive pollen broadcasting (B value was 0.24, 0.13, 0.66, 0.47, respectively, all P<0.05). The higher the disease cognition level of PiAR patients, the stronger their willingness to actively participate in treatment ( R2=0.72, P<0.001). Only 18.89% of AR patients felt satisfied with the treatment effect. Logistic regression analysis showed that in AR patients, the treatment satisfaction rate was significantly higher among those concerned about pollen broadcasting compared to those who were not ( OR=1.83, P<0.001). Conclusions:Currently, the dissemination of pollen broadcasting in China is hindered by various factors such as disease cognition level. The treatment satisfaction among AR patients remains unsatisfactory.
9.Experts consensus on standard items of the cohort construction and quality control of temporomandibular joint diseases (2024)
Min HU ; Chi YANG ; Huawei LIU ; Haixia LU ; Chen YAO ; Qiufei XIE ; Yongjin CHEN ; Kaiyuan FU ; Bing FANG ; Songsong ZHU ; Qing ZHOU ; Zhiye CHEN ; Yaomin ZHU ; Qingbin ZHANG ; Ying YAN ; Xing LONG ; Zhiyong LI ; Yehua GAN ; Shibin YU ; Yuxing BAI ; Yi ZHANG ; Yanyi WANG ; Jie LEI ; Yong CHENG ; Changkui LIU ; Ye CAO ; Dongmei HE ; Ning WEN ; Shanyong ZHANG ; Minjie CHEN ; Guoliang JIAO ; Xinhua LIU ; Hua JIANG ; Yang HE ; Pei SHEN ; Haitao HUANG ; Yongfeng LI ; Jisi ZHENG ; Jing GUO ; Lisheng ZHAO ; Laiqing XU
Chinese Journal of Stomatology 2024;59(10):977-987
Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.
10.Application of Allograft Endometriosis Rat Model in Pharmaco-dynamic Evaluation of GnRH Agonists
Ruihua ZHONG ; Guoting LI ; Wenjie YANG ; Xiangjie GUO ; Jieyun ZHOU ; Yingyi HU ; Qicheng NI ; Ye YANG ; Min ZHANG ; Yan ZHU
Laboratory Animal and Comparative Medicine 2024;44(2):127-138
Objective To establish an allogeneic rat model of endometriosis and to evaluate the effects of gonadotropin-releasing hormone (GnRH) agonist GenSci006 on experimental rat endometriosis. Methods Endometrium from SPF grade donor female SD rats were transplanted onto the abdominal wall of recipient female rats to construct an allogeneic endometriosis model. The rats undergoing sham surgery were divided into the sham group. Three weeks later, the length, width and height of the ectopic endometrium were measured, and the volume of the endometrium (V1) was calculated before drug administration. The modeling rats were randomly divided into four groups: model group, triptorelin group (0.25 mg/kg), GenSci006-1 group (0.125 mg/kg) and GenSci006-2 group (0.25 mg/kg). Each group had 16 rats and received a single dose of the corresponding drug. The sham group and model group were administered an equal volume of solvent. Three weeks after administration, ectopic endometrium was measured to calculate the volume V2 and inhibition rate. The effect of GenSci006 on rat uterus and ovarian tissues was assessed by comparing organ coefficients and changes in pathological sections. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of serum estradiol (E2), progesterone (P4), follicle stimulating hormone (FSH), and luteinizing hormone (LH). Real-time fluorescent quantitative PCR was used to detect the expression of GnRH receptor (GnRHR) mRNA in the hypothalamus and pituitary. Western blot was used to detect the expression of estradiol receptor alpha (ERα), beta (ERβ) and progesterone receptor (PR) in ectopic endometrium. Results Three weeks after administration, compared with the model group, the body weight of rats in the triptorelin and GenSci006-2 groups significantly increased (P < 0.05), while the volume of ectopic endometrium significantly decreased (P < 0.05). Compared with the sham group, the model group showed no significant changes in uterine and ovarian organ coefficients or endometrial thickness (P > 0.05). Compared with the model group, the uterine organ coefficients and endometrial thickness were significantly reduced in the triptorelin and GenSci006-2 groups (P < 0.05). Compared with the sham group, the serum levels of E2, P4, FSH and LH in the model group showed no significant changes (P > 0.05). Compared with the model group, the ovarian organ coefficient and serum P4 levels of rats in the Triptorelin, GenSci006-1, and GenSci006-2 groups were significantly reduced (P < 0.05), while the serum LH levels of rats in the GenSci006-1 group were significantly increased (P < 0.05). However, there were no significant changes in serum E2 and FSH levels in each group (P > 0.05). Compared with the model group, the expression levels of GnRHR mRNA in the pituitary tissue of rats in the triptorelin and GenSci006-2 groups were significantly downregulated (P < 0.05), with no significantly changes in the hypothalamus (P > 0.05). There were no significant changes in the expression level of GnRHR mRNA in the hypothalamus or the protein levels of ERα, ERβ and PR in the ectopic endometrial tissue in any group (P > 0.05). Conclusion The allogeneic endometriosis rat model is a suitable animal model for screening and evaluating drugs for treating endometriosis. The volume of ectopic endometrium, inhibition rate, uterine and ovarian organ coefficients, and serum E2 levels may serve as indicators for detecting drug efficacy.

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