Role of Macrophage Polarization in Chronic Low-grade Inflammation of PCOS Based on Theory of Spleen Being in Charge of Defensive Function / 中国实验方剂学杂志

Polycystic ovary syndrome （PCOS） is a reproductive endocrine disorder characterized by coexisting reproductive dysfunction and glucolipid metabolic disturbance， affecting 8%-13% of women of reproductive age and 3%-11% of adolescent females. Due to the highly heterogeneous clinical features， symptom-oriented individualized strategies are commonly adopted for the treatment of PCOS. Chronic low-grade inflammation is one of the core mechanisms for the occurrence of PCOS. Macrophages， as foundational cells of innate immunity， play an indispensable role in modulating systemic inflammatory responses. The imbalance of macrophage M1/M2 polarization is involved in chronic low-grade inflammation in PCOS via pathways such as activating pro-inflammatory responses， disrupting ovarian tissue repair， stimulating excessive synthesis of androgens， and promoting the occurrence of insulin resistance. Reshaping the phenotype of macrophages might serve as a potential therapeutic strategy for PCOS. Traditional Chinese medicine （TCM） holds that spleen deficiency and phlegm dampness is a crucial pathogenesis of PCOS. The spleen， being in charge of defensive function， plays a key role in ensuring normal physiological functions such as transportation and defense against external pathogen during the occurrence and development of PCOS. The imbalance of macrophage polarization resembles the transition from spleen being in charge of defensive function to spleen losing its defensive role in TCM. Therefore， this paper， for the first time， explores the deep connection between macrophage polarization and the pathogenesis of chronic low-grade inflammation in PCOS from the TCM theory of spleen being in charge of defensive function， providing theoretical support and new research directions for the treatment and drug research of PCOS.

Rosiglitazone improves ovarian dysfunction of rats with chronic low-grade inflammation induced by lipopolysaccharide / 第二军医大学学报

Objective: To detect the expression of peroxisome proliferator-activated receptor (PPAR) in ovarian tissues of rats with chronic low-grade inflammation, and to explore the effect of PPAR-γ agonist rosiglitazone on ovarian dysfunction induced by chronic low-grade inflammation. Methods: A chronic low-grade inflammation model of rats was established by intraperitoneal injection of lipopolysaccharide (LPS). Two hundred rats were randomly assigned to control group (NS group) and chronic low-grade inflammation group (LPS group), and the rats were intraperitoneally injected with normal saline and LPS, respectively. The ovarian function of rats was assessed by detecting the serum levels of estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH), and anti-Müllerian hormone (AMH) during different stages of the estrus cycle (proestrus, estrus, metestrus and diestrus). The protein expression levels of PPAR-α, PPAR-γ and PPAR-γ in ovarian tissues were detected using Western blotting. Eighty rats of each group were randomly divided into two subgroups, which were administered intragastrically by normal saline and rosiglitazone, respectively. Fourteen days after intragastric administration, the levels of proinflammatory cytokines, including interleukin (IL)-1β, IL-6 and tumor necrosis factor α (TNF-α), in ovarian tissues and ovarian function of rats in each subgroup were observed during different stages of the estrus cycle. Results: Compared with the NS group, during different stages of the estrus cycle, the serum levels of E2 and AMH of rats in the LPS group were significantly decreased (all P < 0.05), while the serum levels of FSH and LH were significantly increased (all P < 0.05). During different stages of the estrus cycle, the expression levels of PPAR-γ in ovarian tissues were significantly decreased in the LPS group compared with the NS group (all P < 0.05), while the expression levels of PPAR-α and PPAR-δ were not significantly different between the two groups (all P < 0.05). Compared with the intraperitoneal injection of LPS intragastric administration of normal saline subgroup, during different stages of the estrus cycle, the expression levels IL-1β, IL-6 and TNF-α in ovarian tissues of rats were significantly decreased in the intraperitoneal injection of LPS intragastric administration of rosiglitazone subgroup (all P < 0.05), the serum levels of E2 and AMH were significantly increased (all P < 0.05), and the serum levels of FSH and LH were significantly decreased (all P < 0.05). Conclusion: PPAR-γ agonist rosiglitazone can attenuate LPS-induced chronic low-grade inflammatory and improve ovarian function in rats.

Relation of plasma galectin-3 level with parameters of chronic inflammation and insulin resistance in the patients with polycystic ovary syndrome / 中华内分泌代谢杂志

A total of 108 subjects were enrolled in this study, including 21 healthy subjects(control group), 34 non-obese patients with polycystic ovary syndrome [PCOS1 group, body mass index(BMI)<25 kg/m2], 32 obese patients with PCOS(PCOS2 group, BMI≥25 kg/m2), and 21 simple obese patients whose age and BMI matched with PCOS2(OB group). BMI, waist-hip ratio(WHR), fasting plasma glucose(FPG), postprandial 2h plasma glucose(2hPG), HbA1C, fasting insulin(FINS), postprandial 2h insulin(2hINS), sex hormones, and lipid parameters were determined. The status of insulin resistance was assessed by homeostasis model assessment for insulin resistant index(HOMA-IR)and insulin sensitivity index(ISI). Levels of plasma galectin-3 and interleukin-6(IL-6)were detected by ELISA. The results showed that the plasma level of galectin-3 was significantly higher in PCOS group than those in control and OB groups(all P<0.05). Moreover, the level of galectin-3 was also higher in OB group compared with control group, while galectin-3 level in PCOS2 group was higher than that in PCOS1 group(all P<0.05). After adjusted by age, BMI, and WHR, correlation analysis showed that the level of galectin-3 was positively correlated with FPG, 2hPG, FINS, HOMA-IR, highly-sensitive C-reactive protein, and IL-6, while negatively correlated with ISI. A multiple linear regression analysis revealed that the plasma galectin-3 concentration was independently associated with IL-6, HOMA-IR, and BMI(all P<0.05). These data suggest that plasma galectin-3 is closely associated with glucose metabolism, chronic inflammation, and insulin resistance, which may be involved in the pathogenesis of PCOS. (Chin J Endocrinol Metab, 2018, 34: 578-582)

Knockdown of growth hormone receptor prevents growth hormone in-duced inflammatory cytokine production in 3T3-L1 adipocytes / 中国病理生理杂志

AIM:To investigate the effect of growth hormone receptor(GHR) knockdown on nuclear factor-κB (NF-κB) activity and inflammatory cytokine production stimulated by growth hormone (GH) in 3T3-L1 adipocytes. METHODS:The specific siRNA for GHR was transfected into 3T3-L1 adipocytes to silence GHR expressions. The effects of GH on NF-κB activation and inflammatory cytokine production in 3T3-L1 adipocytes transfected with siRNA-GHR or siRNA-control were measured by dual-luciferase system analysis,real-time RT-PCR and ELISA. RESULTS:The protein expression of GHR was diminished after transfection with GHR specific siRNA. Dual-luciferase reporter system analysis re-vealed that GHR knockdown resulted in attenuation of GH-stimulated NF-κB activation in the 3T3-L1 adipocytes. GHR knockdown ameliorated the GH-induced production of inflammatory cytokines TNF-α,IL-1β,IL-6,MCP-1 and MIP-1α in the 3T3-L1 adipocytes. CONCLUSION:Knockdown of GHR might be efficacious to prevent GH-induced inflammatory re-sponses in the 3T3-L1 adipocytes.