Abstract. Pain is the most pronounced complaint of women with endometriosis, however the underlying mechanism is still poorly understood. In the present study, the authors evaluate the effect of transient receptor potential vanilloid type 1 (TRPV1) of dorsal root ganglia (DRG) on endometriosis-associated pain. A total of 36 SD rats were randomly divided into a sham group (n=9) and a Model group (n=27), accepted auto-transplanted pieces of fat or uterus to the pelvic cavity. At 4 weeks, the Model group was randomly subdivided into the following groups: ENDO group (no treatment, n=9), BCTC group (Model + BCTC, an antagonist of TRPV1, n=9), Vehicle group (Model + cyclodextrin, the vehicle of BCTC, n=9). Tail-flick test was performed prior to surgery, 1 h prior to and following treatment of BCTC or cyclodextrin. The expression of TRPV1, substance P (SP), calcitonin gene-related peptide (CGRP) in L1-L6 DRG was measured via immunohistochemistry, western blotting and RT-qPCR. The results indicated that the Model group exhibited a significant decrease in tail flick latency compared to pre-surgical baseline, and the expression of TRPV1, SP, CGRP protein and mRNA in L1-L6 DRG significantly increased compared to the sham group. BCTC significantly improved tail flick latency, and downregulated the expression of TRPV1, SP and CGRP protein and mRNA levels in L1-L6 DRG compared to ENDO group. However, there were no significant differences of those in Vehicle group compared with the ENDO group. Taken together, the current study provides evidence that TRPV1 expressed in DRG may serve an important role in endometriosis-associated pain. IntroductionEndometriosis, a disease in which endometrium-like tissue grows outside of the uterine cavity, has been estimated to affect 2 to 10% of reproductive-age women (1). The chief complaint of women with endometriosis is pain, which negatively affects quality of life. However, the pathogenesis of endometriosis-related pain, in particularly, chronic pain remains elusive and needs further investigation.It is universally accepted that peritoneal inflammation serves an important role in pain production (2). In previous years, the concept of neuropathic pain has been recognized and given much concern and study (3,4). Numerous studies have indicated the presence of nerve fibers with neurotransmitters immunoreactive cells in ovarian and deep infiltrating endometriosis, such as CGRP and SP (5-7). Therefore, the research is crucially needed to explore how the nerve fibers in endometriosis lesions influence dorsal root neurons and brain to evoke pain. The nociceptive sensors in DRG neurons are the first station in the transmission of pain and are, thereby, a research hotspot for pain study (3,8). An increasing number of studies revealed that transient receptor potential vanilloid type 1 (TRPV1) serves an important role in initiating neurogenic inflammation and pain sensitization (9,10). TRPV1 is a member of non-selective cation channels, which mediates responses to pain-inducing stimuli, such as acid (...
The present study was designed to elucidate the underlying mechanisms of Bao Gui capsule (BGc) against hyperandrogenism, insulin resistance and leptin resistance of PcoS. letrozole was used to induce a PcoS model in rats, which were then randomly divided into four groups (n=9): control, Model, high-dose BGc (BGc-H) and low-dose BGc (BGc-l) group. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (lH), testosterone (T), estradiol (e 2 ), insulin, leptin, and interleukin (il)-1β, il-6 and tumor necrosis factor-α (TnF-α) in the hypothalamus were determined by eliSa. Protein levels of cytochrome P450c17α and cytochrome P450 aromatase (P450arom) in ovaries were determined by immunohistochemistry and western blot analysis. additionally, the expression of GluT4 in uterus and muscle tissue, and nF-κB, iKKβ and SocS3 mrna levels in the hypothalamus were evaluated. BGC significantly reduced body weight gain and decreased serum levels of lH/FSH, T, log T/e 2 , insulin and leptin compared with the PcoS model rats. Furthermore, BGc markedly reduced the expression of P450c17α and significantly increased the expression of P450arom in ovaries, and increased the expression of GluT4 in uterus and muscle tissues. BGc also effectively reduced the level of il-6 and TnF-α, and the expression of iKKβ, nF-κB and SocS3 in the hypothalamus of PcoS model rats. These results suggest that BGc may effectively improve hyperandrogenism, insulin resistance, endometrial receptivity and the low-grade chronic inflammation in the hypothalamus.
Methazolamide (MTZ), a carbonic anhydrase inhibitor, has been shown to inhibit cardiomyocyte hypertrophy and exert a hypoglycemic effect in patients with type 2 diabetes mellitus and diabetic db/db mice. However, whether MTZ has a cardioprotective effect in the setting of diabetic cardiomyopathy is not clear. We investigated the effects of MTZ in a mouse model of streptozotocin-induced type 1 diabetes mellitus (T1DM). Diabetic mice received MTZ by intragastric gavage (10, 25, or 50 mg/kg; daily for 16 weeks). In the diabetic group, MTZ significantly reduced both random and fasting blood glucose levels and improved glucose tolerance in a dose-dependent manner. MTZ ameliorated T1DM-induced changes in cardiac morphology and dysfunction. Mechanistic analysis revealed that MTZ blunted T1DM-induced enhanced expression of β-catenin. Similar results were observed in neonatal rat cardiomyocytes (NRCMs) and adult mouse cardiomyocytes treated with high glucose or Wnt3a (a β-catenin activator). There was no significant change in β-catenin mRNA levels in cardiac tissues or NRCMs. MTZ-mediated β-catenin downregulation was recovered by MG132, a proteasome inhibitor. Immunoprecipitation and immunofluorescence analyses showed augmentation of AXIN1–β-catenin interaction by MTZ in T1DM hearts and in NRCMs treated with Wnt3a; thus, MTZ may potentiate AXIN1–β-catenin linkage to increase β-catenin degradation. Overall, MTZ may alleviate cardiac hypertrophy by mediating AXIN1–β-catenin interaction to promote degradation and inhibition of β-catenin activity. These findings may help inform novel therapeutic strategy to prevent heart failure in patients with diabetes mellitus.
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