Interstitial Macrophages Drive Pulmonary Arteriole Medial Fibrosis in PAH

间质巨噬细胞驱动肺动脉高压中的肺小动脉中层纤维化

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Abstract

Exposure to elevated environmental temperatures during the peripubertal period of male small ruminants fosters restricted growth of secondary sex characteristics, denoting poor reproductive performance in sexual maturity and therefore contributing to economic and productive loss. N-carbamylglutamate (NCG), a direct precursor to the amino acid arginine, has been shown to promote growth, feed efficiency, as well as reproductive performance in ruminants. Melatonin, a neuroendocrine hormone that works to control circadian rhythms, has also shown to elicit vasodilation and vasoconstriction responses in blood vessels to alleviate the effects of heat stress on ruminants. Although, the coupled supplementation of melatonin and NCG in peripubertal male lambs experiencing elevated levels of heat stress has not yet been comprehensively studied. Thus, the objectives of this study were to investigate the influence of heat stress and the supplementation of NCG and melatonin on macroscopic testicular morphometrics and testicular histological appearance in 24 commercial Dorper rams. After a 2-week acclimation period, the 4-month-old lamb rams were assigned into 1 of 4 groups based on body weight in a 2 x 2 factorial design. The groups consisted of a cooled environment (CL-CON; n = 5), a heat stressed environment (HS-CON; n = 6), and a cooled or heat stressed environment supplemented with 1.4g/h/d of NCG and 8mg melatonin/h/d (CL-NCGMEL, n = 5; HS-NCGMEL; n = 6). On day 42 posttreatment, rams were slaughtered and the testicles were collected to determine testicular weight and scrotal circumference. Data were analyzed utilizing the MIXED procedure of SAS v 9.4 including environment and dietary treatments as fixed effects and their corresponding interactions. An environment by dietary treatment interaction was observed for testicular weight (P = 0.0343), where HS-CON lambs had lower testicular weights (427.73 ± 36.76 g) compared with CL-CON and HS-NCGMEL (651.58 ± 51.09 vs. 557.22 ± 34.48 g, respectively). Nevertheless, no significant difference was observed between the testicular weight of CL-CON and HS-NCGMEL lamb rams (P > 0.05). Additionally, an environment by dietary treatment interaction was observed where testicular circumference (P = 0.043) in HS-NCGMEL animals was increased compared to control (30.422±0.85 vs. 27.375±0.94 cm). Similarly, The HS-CON had lower (P = 0.0383) testicular diameter (16.286±0.449 cm) compared with CL-CON and HS-NCGMEL (18.57±0.62 and 18.400±0.43 cm). Lastly, epididymal weights of the HS-CON group were decreased (P = 0.033) as compared to the HS-NCGMEL group (14.22±1.73 vs 19.69 ±1.57 g, respectively). The significant increase in testicle weight, circumference, diameter, and epididymal weight of HS-NCGMEL rams may indicate increased growth efficiency within secondary sex characteristics within the peripubertal growth period.

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