Qingxuan Jiangya Decoction Mitigates Renal Interstitial Fibrosis in Spontaneously Hypertensive Rats by Regulating Transforming Growth Factor- β 1/Smad Signaling Pathway

Abstract

Qingxuan Jiangya Decoction (QXJYD) is a traditional Chinese medicine commonly used in the clinical treatment of hypertension. Earlier studies had shown that QXJYD could inhibit the elevation of blood pressure in spontaneously hypertensive rats (SHRs) and prevent remodeling of arterial vessels. This study examines the therapeutic efficacy of QXJYD against elevated blood pressure using the SHR model, as well as the mechanisms behind its antihypertensive activity and protection against renal fibrosis. The results showed that QXJYD significantly attenuated the increase in blood pressure in SHRs and mitigated the development of renal interstitial fibrosis. In addition, QXJYD also robustly decreased the excess accumulation of extracellular matrix and attenuated the elevated expression of MMPs. The antihypertensive effects and renal protection of QXJYD were determined to be strongly associated with inhibition of TGF-β1/Smad signaling pathway.

Figure 1

Effect of QXJYD treatment on blood pressure. (a) Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), and (b) body weight were measured in spontaneously hypertensive rats (SHR, QXJYD) and Wistar Kyoto (WKY) rats (n = 10). All values were represented as mean ± SD. ^∗p < 0.05, compared to WKY group; ^∗∗p < 0.05, compared to SHR group.

Figure 2

Effect of QXJYD treatment on mitigated damage of glomerulus. Histopathological changes of glomerulus in each group (n = 6) were observed by Harris Hematoxylin and Eosin (H&E) staining. Images were representatives taken at a magnification of 40x (top, scale bar = 200 μm).

Figure 3

Effect of QXJYD treatment on the expression of collagen fiber in SHRs. (a) Representative image of Masson trichrome staining of kidney. (b) The Masson trichrome-positive tubulointerstitial area (blue) relative to the whole area from 6 random kidney fields was evaluated. Data are represented as the mean ± SEM (n = 6). Immunohistochemical analysis was performed to determine the protein expression of Collagen I (c), Collagen III (d), and Collagen IV (e) in renal interstitial from each group (n = 6). Images were representatives taken at a magnification of 40x. (f) Quantification of the mean expressions of Collagen I, Collagen III, and Collagen IV protein. All values were represented as the mean ± SD; ^∗p < 0.05 compared to WKY group and ^∗∗p < 0.05 compared to SHR group.

Figure 4

Effect of QXJYD treatment on the mRNA expression in SHRs. Q-PCR was performed to determine the mRNA expression of TGF-β1, Smad3 (a); MMP-2, MMP-9, and TIMP-1 (b); and Collagen I, Collagen III, and Collagen IV (c) in kidney issue from each group (n = 3). All values were represented as the mean ± SD; ^∗p < 0.05 compared to WKY group and ^∗∗p < 0.05 compared to SHR group.

Figure 5

Effect of QXJYD treatment on the protein expression in SHRs. Western blot was performed to determine the protein expression of TGf-β1 (a), Smad2/3 (b), Smad4 (c), and MMP-2 and MMP-9 (d) in kidney issue from each group (n = 3). All values were represented as the mean ± SD; ^∗p < 0.05 compared to WKY group and ^∗∗p < 0.05 compared to SHR group.