1.Effect and Mechanism of Xiao Qinglongtang Against Right Ventricular Dysfunction in Rats with Pulmonary Arterial Hypertension Induced by Monocrotaline
Lei QI ; Huifei ZHANG ; Ling GONG ; Jifu HE ; Wenjing CHEN ; Weipin NIU ; Xiao LI ; Yuehua JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):11-19
ObjectiveThis study aimed to establish a monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) rat model to systematically evaluate the protective effect of Xiao Qinglongtang (XQLT) on right cardiac function in model rats and further elucidate the underlying regulatory mechanism. MethodsSixty male SD rats were randomly assigned to the normal group, model group, XQLT low-, medium-, and high-dose groups (XQLT-L/M/H), and the beraprost sodium tablet group (BST). Except for the normal group, rats in all other groups were given a single subcutaneous injection of MCT (60 mg·kg-1) to induce PAH. Three weeks after injection, rats in the XQLT-L/M/H groups were administered XQLT intragastrically at 3.07, 6.14, 12.28 g·kg-1·d-1, respectively. Rats in the BST group received beraprost sodium at 12.6 μg·kg-1·d-1, and rats in the model group received an equal volume of saline. All treatments lasted for 3 weeks. Right ventricular systolic pressure (RVSP) was measured by right ventricular catheterization. Cardiac function was assessed by echocardiography. The right ventricle was weighed to calculate the right ventricular hypertrophy index (RVHI). Hematoxylin-eosin (HE) staining, Masson staining, and transmission electron microscopy were used to observe myocardial morphology. Serum metabolomic changes were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Data-independent acquisition (DIA) proteomics was used to detect differentially expressed (DE) proteins in the right ventricle, and Western blot was used to measure the expression of uncoupling protein 3 (UCP3), phosphatidylinositol 3-kinase catalytic subunit p110α (PIK3CA), L1 cell adhesion molecule (L1CAM), and quinone oxidoreductase (CRYZ). UPLC-MS/MS was used to analyze the chemical components of XQLT. ResultsCompared with the normal group, the model group showed significantly increased RVSP and RVHI (P<0.05), along with pathological changes in myocardial morphology. Compared with the model group, all XQLT-treated groups exhibited reductions in RVSP and RVHI as well as significant improvements in cardiac function and myocardial morphology. Among the XQLT groups, XQLT-M showed the most pronounced effects (P<0.05), comparable to the BST group. Serum metabolomics revealed 105 differential metabolites in the XQLT groups versus the model group [variable importance in projection (VIP) >1, P<0.05], including 58 upregulated and 47 downregulated metabolites. KEGG enrichment analysis indicated that XQLT intervention downregulated phenylalanine metabolism (P<0.01) and upregulated unsaturated fatty acid biosynthesis (P<0.05). Proteomics analysis showed that 982 DE proteins were identified in the MCT groups versus the normal group, including 455 upregulated and 527 downregulated proteins (|fold change (FC)| >1.3, P<0.05). Compared with the model group, 237 DE proteins were identified in the XQLT groups, including 124 upregulated and 113 downregulated proteins (|FC| >1.3, P<0.05), with 57 overlapping DE proteins. KEGG enrichment suggested that XQLT mainly modulated pathways related to mineral absorption, ribosomal biogenesis, peroxisomes, glycolysis/gluconeogenesis, spliceosomes, and thyroid hormone signaling. Western blot analysis showed that, compared with the model group, XQLT increased the expression of UCP3, PIK3CA, and L1CAM, while decreasing the expression of CRYZ (P<0.05). ConclusionXQLT exerts a protective effect on right heart function in MCT-induced PAH rats, and its mechanism is associated with maintaining myocardial homeostasis and alleviating right ventricular remodeling.
2.Effects of Tongxin Huoqian Decoction on fibrosis in mice with adenomyosis model
Yinuo CHEN ; Yinuo ZHANG ; Xin WANG ; Zilu WANG ; Yu ZHANG ; Wei SHI ; Weipin NIU
International Journal of Traditional Chinese Medicine 2025;47(12):1687-1694
Objective:To study the effects of Tongmai Huazheng Decoction on the fibrosis of lesions in mice with adenomyosis (AM); To explore its mechanism.Methods:The ICR mouse model of adenomyosis was established by using tamoxifen modeling method. The 30 mice successfully modeled were divided into model group, Tongmai Huazheng Decoction group and progesterone group according to the random number table method with 10 mice in each group, and 10 female mice were set as the blank group. Tongmai Huazheng Decoction group was intragastrically administered with Tongmai Huazheng Decoction 30.47 g/kg, once/d; The gestrinone group was intragastrically administered with gestrinone suspension 0.32 mg/kg, twice a week; the blank group and model group were intragastrically administered with 0.1 ml/10 g normal saline, once a day. After 8 weeks of intervention, HE staining was used to observe the pathological changes of uterine tissue; Masson staining was used to observe the degree of uterine tissue fibrosis; immunofluorescence method was used to detect the protein expressions of CollagenⅠ, CollagenⅢ and fibronectin in uterine tissue of each group; Western bolt method was used to detect the protein expressions of TGF-β1 and α-smooth muscle actin (α-SMA) in each group.Results:Compared with the model group, the ratio of collagen fiber area in uterine tissue in Tongmai Huazheng Decoction group and progesterone group decreased ( P<0.05), the immunofluorescence intensity of CollagenⅠ, CollagenⅢ and Fibronectin decreased ( P<0.05), and the expressions of TGF-β1 and α-SMA proteins decreased ( P<0.05). Conclusion:Tongmai Huazheng Decoction can reduce the ratio of collagen fiber area in the uterus of mice with adenomyosis model, downregulate the expression of CollagenⅠ, Collagen Ⅲ, Fibronectin, TGF-β1, and α-SMA proteins, alleviate the degree of fibrosis in adenomyosis lesions, and thus inhibit or slow down disease progression.

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