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    • Effects of exercise during pregnancy on renal fibrosis and AngⅡ/TGF-β1/CTGF signaling pathway in offspring of spontaneously hypertensive rats

      2025, 33(1):16-23.

      Keywords:exercise during pregnancy spontaneous hypertension offspring renal fibrosis AngⅡ/TGF-β1/CTGF signaling pathway
      Abstract (51)HTML (0)PDF 15.03 M (151)Favorites

      Abstract:Aim To explore the effects of exercise during pregnancy on renal structure, function and angiotensin Ⅱ (Ang Ⅱ)/transforming growth factor-β1 (TGF-β1)/connective tissue growth factor (CTGF) signaling pathway in 3-month-old offspring of spontaneously hypertensive rats (SHR), the aim of this study was to provide experimental basis for early intervention of hypertension and protection of key target organs. Methods After mating SHR and WKY rats, pregnant rats were randomly divided into sedentary group (p-WKY-SED, p-SHR-SED) and exercise group (p-WKY-EX, p-SHR-EX). Blood pressure, serum urea nitrogen and creatinine were measured by caudal artery non-invasive blood pressure system and colorimetry in 3-month-old offspring rats. HE staining, Masson staining, ELISA and Western blot were used to detect the renal structure, collagen volume fraction, AngⅡ concentration, renin-angiotension-aldosterone system (RAAS) and protein expression related to fibrogenic signal pathway in 3-month-old rats. Results (1) The systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) of offspring rats in p-SHR-SED group were significantly higher than those in p-WKY-SED group. The SBP, DBP and MAP of SHR male offspring rats were significantly decreased by exercise during pregnancy (P<0.05), but had no effect on the female offspring rats (P>0.05). (2) There was no significant difference in serum urea nitrogen and creatinine among the groups (P>0.05). (3) The glomerular volume and the collagen volume fraction in p-SHR-SED group were significantly higher than those in p-WKY-SED group (P<0.05), and the glomerular volume and the collagen volume fraction in p-SHR-EX group were significantly lower than those in p-SHR-SED group (P<0.05). (4) Renal AngⅡ level of offspring rats in p-SHR-SED group was significantly higher than that in p-WKY-SED group, and renal AngⅡ level of offspring rats in p-SHR-EX group was significantly lower than that in p-SHR-SED group (P<0.05). (5) The expression levels of angiotensinⅡ type 1 receptor (AT1R), TGF-β1 and CTGF protein in p-SHR-SED group were significantly higher than those in p-WKY-SED group (P<0.05), while the expression levels of angiotensin converting enzyme 2 (ACE2), angiotensinⅡ type 2 receptor (AT2R) and MasR protein in p-SHR-SED group were significantly lower than those in p-WKY-SED group (P<0.05). Conclusion (1) Exercise during pregnancy can significantly decrease the blood pressure of 3-month-old male offspring rats of hypertensive rats, but has no significant effect on that of 3-month-old female offspring. (2) Exercise during pregnancy may reduce renal fibrosis in 3-month-old female/male offspring of hypertensive rats by regulating RAAS balance and inhibiting AngⅡ /TGF-β1/CTGF signaling pathway.

    • Effect of Apelin-13 on hypertensive renal fibrosis and mechanism study

      2017, 25(1):37-42.

      Keywords:Apelin-13 Hypertension Renal fibrosis Autophagy Autophagy related protein
      Abstract (985)HTML (0)PDF 5.70 M (1075)Favorites

      Abstract:Aim To observe the effect of putative receptor protein related to the angiotensin receptor AT1 (APJ) agonist Apelin-13 on the hypertensive renal fibrosis and to explore the possible mechanism in spontaneously hypertensive rat (SHR). Methods Male SHRs of 12 weeks old were randomly divided into control group and 1 μg/(kg·d) Apelin-13 group, 10 μg/(kg·d) Apelin-13 group, 100 μg/(kg·d) Apelin-13 group. The rats were administrated with Apelin-13 by tail vein for 12 weeks. 24 h urine protein was continuously measured. Serum creatinine and urea nitrogen were measured. Systolic blood pressure (SBP) was continuously measured by tail method. Histological change of kidney was observed by HE staining and Masson staining. The expressions of autophagy related protein microtubule-associated protein light chain-3 (LC3), Beclin-1 and the autophagy substrates p62 in the kidney were determined by Western blot. Results Compared with control group, SBP, 24 h urine protein, serum creatinine and urea nitrogen, renal injury score and collagen volume fraction were significantly decreased in dose-dependent manner in 10 μg/(kg·d) Apelin-13 group and 100 μg/(kg·d) Apelin-13 group (all P<0.05). The edema of renal tubular epithelial cells was alleviated, the interstitial collagen deposition was decreased, and the degree of renal interstitial fibrosis was decreased in 10 μg/(kg·d) Apelin-13 group and 100 μg/(kg·d) Apelin-13 group. Compared with control group, LC3-Ⅱ expression, LC3-Ⅱ/LC3-Ⅰ ratio and Beclin-1 expression were singificantly increased and p62 expression was singificantly decreased in kidney in dose-dependent manner in 10 μg/(kg·d) Apelin-13 group and 100 μg/(kg·d) Apelin-13 group (all P<0.05). Conclusion Apelin-13 inhibits the progression of hypertensive renal fibrosis, and its mechanism may be related to the inhibition of autophagy by Apelin-13.

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