Exogenous H2S delays premature myocardial aging and inhibits myocardial fibrosis in uremic rats by upregulating SIRT1

doi:10.11958/20220662

Abstract

Abstract:

Objective To investigate the effect of hydrogen sulfide (H₂S) on premature myocardial aging and myocardial fibrosis in uremic rats. Methods Forty-eight male SD rats were randomly divided into the sham operation group (Sham group), the model group (uremic cardiomyopathy, UCM group), the H₂S treatment group (UCM+H₂S group) and the H₂S group. Rats in the UCM group and the UCM+H₂S group were modeled by the classic 5/6 nephrectomy method. After the model was established, rats in the UCM+H₂S group and the H₂S group were injected with sodium hydrosulfide (NaHS, 50 μmol/kg) every day for 8 weeks, while the Sham group and the UCM group were injected with the same amount of normal saline. Left ventricular shortening rate (LVFS) was measured by cardiac ultrasound. Masson staining was used to evaluate myocardial fibrosis, and collagen volume fraction (CVF) was calculated. The expression of type Ⅲ collagen in myocardium was detected by immunohistochemistry. β -galactosidase staining was used to detect senescent myocardial cells. The expression levels of SIRT1, NLRP3, interleukin (IL) -1β, P21, P19 and P53 proteins in myocardium were measured by Western blot assay. Results Compared with the Sham group, LVFS was significantly decreased in the UCM group, the relative expression levels of CVF, type Ⅲ collagen and the positive rate of β -galactosidase staining were increased, the expressions of NLRP3, IL-1β, P19, P21 and P53 were increased, and the expression of SIRT1 protein was decreased (P<0.05). Compared with the UCM group, the relative expression levels of CVF, type Ⅲ collagen and positive staining rate of β-galactosidase were decreased in the UCM+H₂S group, and the protein expressions of NLRP3, IL-1β, P19, P21 and P53 were decreased, while the protein expression of SIRT1 was increased (P<0.05). Conclusion Exogenous H₂S can improve myocardial fibrosis in uremic rats, and the mechanism may be related to the upregulation of SIRT1 and the inhibition of premature myocardial senescence.

Key words: hydrogen sulfide, aging, uremia, NLR family, pyrin domain-containing 3 protein, silent information regulator-1, myocardial fibrosis

CLC Number:

R542.2+3

Figures/Tables 7

Tab.1 Comparison of serum BUN and Scr between the four groups

组别	n	BUN（mmol/L）	Scr（μmol/L）
Sham组	12	11.11±2.43	31.75±6.02
UCM组	8	25.09±7.04^a	109.50±12.45^a
UCM+H₂S组	9	23.13±6.23^a	106.20±11.69^a
H₂S组	11	10.67±1.94	32.14±5.61
F		27.000^＊	158.100^＊

Fig.1 Ultrasound image of rat heart function in each group

Fig.2 Masson staining of collagen fibers in myocardial tissue of rats in each group (×400)

Fig.3 Expression of type Ⅲ collagen in myocardial tissue of rats in each group (immunohistochemical staining, ×400)

Fig.4 The aging level of myocardial tissue of rats in each group (β -galactosidase staining, ×400)

Fig.5 The protein expression levels of SIRT1, P21, P19，P53, NLRP3 and IL-1β in myocardial tissue of rats in each group

Tab.3 Comparison of SIRT1, P21, P19, P53, NLRP3 and IL-1β protein expression levels in myocardial tissue of rats between the four groups

组别	SIRT1	P21	P19
Sham组	0.87±0.07	0.69±0.02	1.18±0.08
UCM组	0.69±0.05^a	0.93±0.04^a	1.46±0.03^a
UCM+H₂S组	0.83±0.04^b	0.68±0.02^b	1.25±0.03^b
H₂S组	0.83±0.01	0.69±0.02	1.29±0.04
F	6.381^＊	51.420^＊	14.150^＊
组别	P53	NLRP3	IL-1β
Sham组	0.57±0.01	0.68±0.03	0.79±0.07
UCM组	0.79±0.02^a	0.89±0.04^a	1.16±0.10^a
UCM+H₂S组	0.60±0.01^b	0.84±0.02^b	0.92±0.08^b
H₂S组	0.59±0.01	0.69±0.04	0.81±0.06
F	96.370^＊	23.890^＊	11.980^＊

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Exogenous H₂S delays premature myocardial aging and inhibits myocardial fibrosis in uremic rats by upregulating SIRT1

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