Effects of dose and timing of adipose-derived stem cell transplantation on pulmonary arterial pressure in monocrotaline-induced pulmonary arterial hypertension in rats

doi:10.3877/cma.j.issn.2095-1221.2018.06.001

Abstract

Abstract:

Objective

To investigate the effect of dose and timing of adipose-derived stem cells (ADSC) transplantation on pulmonary arterial pressure in monocrotaline (MCT) -induced pulmonary arterial hypertension (PAH) in rats.

Methods

(1) MCT-induced PAH in rats: 48 male SD rats were injected intraperitoneally with normal saline, 20 mg/kg, 30 mg/kg and 40 mg/kg MCT respectively. Mean pulmonary arterial pressure (mPAP) was determined by right heart catheterization and right ventricular hypertrophy index (RVHI) was detected by weighting method at 4 and 8 weeks after MCT injection. (2) Dose of ADSC: male SD rats were administrated with 40 mg/kg MCT (n = 30) and normal saline (n = 30). Normal saline or different numbers of ADSC (0.5×10⁶, 1.0×10⁶, 3.0×10⁶, 5.0×10⁶) were injected through jugular vein at 1 week after intraperitoneal injection of MCT. mPAP and RVHI were detected at 3 weeks after ADSC transplantation. (3) Timing of ADSC transplantation: 30 male SD rats were administrated with 40 mg/kg MCT (n = 30) and normal saline (n = 6). One day, 1 or 2 weeks after intraperitoneal injection of 40 mg/kg MCT, 1.0×10⁶ ADSC were transplanted into the rats. mPAP and RVHI were detected at 4 weeks after MCT injection. Differences among groups were compared using one-way or two-way analysis of variance, and pairwise comparison was performed using LSD test.

Results

(1) 4 weeks after intraperitoneal injection of 30 or 40 mg/kg MCT, both mPAP and RVHI increased [mPAP (mm Hg): 24.89±3.31, 27.19±2.11 vs 15.80±0.42, P < 0.05; RVHI: 0.42±0.06, 0.47±0.04 vs 0.25±0.02, P < 0.05)]. 8 weeks after MCT injection, mPAP and RVHI returned to normal in the 20 and 30 mg/kg MCT groups. All rats died in the 40 mg/kg MCT group. (2) Both mPAP and RVHI in the 40 mg/kg MCT group elevated. 3 weeks after transplantation of 1.0×10⁶ ADSC, mPAP declined (27.19±1.73) mmHg vs (17.24±0.66) mmHg (P < 0.05). However, mPAP did not decrease in rats given 0.5×10⁶, 3.0×10⁶ or 5.0×10⁶ ADSC. (3) 1 or 2 weeks after intraperitoneal injection of 40 mg/ kg MCT, mPAP reduced in PAH rats given 1.0×10⁶ ADSC.

Conclusions

4 weeks after a single intraperitoneal injection of 40 mg/kg MCT, a stable PAH rat model could be established. 1 or 2 weeks after intraperitoneal injection of 40 mg/kg MCT, transplantation of 1.0×10⁶ ADSC could effectively reduce mPAP in PAH rats.

Key words: Adipose tissue-derived stem cell, Pulmonary arterial hypertension, Monocrotaline, Mean pulmonary arterial hypertension

Wuhong Zheng, Li Luo, Ling Li, Guili Lian, Changsheng Xu, Huajun Wang, Liangdi Xie. Effects of dose and timing of adipose-derived stem cell transplantation on pulmonary arterial pressure in monocrotaline-induced pulmonary arterial hypertension in rats[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2018, 08(06): 321-327.

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Figures/Tables 5

References 19

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分组	mPAP（mmHg）		RVHI
分组	4周	8周	4周	8周
对照组	15.80±0.42	15.07±1.04	0.25±0.02	0.25±0.01
20 mg/kg MCT	21.51±2.05	18.22±0.91	0.36±0.05	0.30±0.03
30 mg/kg MCT	24.89±3.31^a	18.60±1.06	0.42±0.06^a	0.32±0.04
40 mg/kg MCT	27.19±2.11^a	-	0.47±0.04^a	-
F值	5.558	3.774	5.062	1.991
P值	0.007	0.049	0.011	0.187

分组	mPAP（mmHg）		RVHI
分组	4周	8周	4周	8周
对照组	15.80±0.42	15.07±1.04	0.25±0.02	0.25±0.01
20 mg/kg MCT	21.51±2.05	18.22±0.91	0.36±0.05	0.30±0.03
30 mg/kg MCT	24.89±3.31^a	18.60±1.06	0.42±0.06^a	0.32±0.04
40 mg/kg MCT	27.19±2.11^a	-	0.47±0.04^a	-
F值	5.558	3.774	5.062	1.991
P值	0.007	0.049	0.011	0.187

ADSC数量	动物数（只）	mPAP（mmHg）		RVHI
ADSC数量	动物数（只）	对照组	PAH	对照组	PAH
0	6	15.46±0.81	27.19±1.73^a	0.25±0.01	0.46±0.03^a
0.5×10⁶	5	16.32±1.39	25.56±1.75^a	0.25±0.01	0.45±0.04^a
1.0×10⁶	5	16.79±1.19	17.24±0.66^b	0.26±0.04	0.42±0.01^a
3.0×10⁶	5	16.45±2.08	28.80±5.81^a	0.27±0.04	0.48±0.07^a
5.0×10⁶	6	16.63±0.91	29.79±2.20^a	0.25±0.01	0.50±0.05^a
F值		2.055	40.88	0.2661	83.58
P值		0.100	< 0.001	0.898	< 0.001

ADSC数量	动物数（只）	mPAP（mmHg）		RVHI
ADSC数量	动物数（只）	对照组	PAH	对照组	PAH
0	6	15.46±0.81	27.19±1.73^a	0.25±0.01	0.46±0.03^a
0.5×10⁶	5	16.32±1.39	25.56±1.75^a	0.25±0.01	0.45±0.04^a
1.0×10⁶	5	16.79±1.19	17.24±0.66^b	0.26±0.04	0.42±0.01^a
3.0×10⁶	5	16.45±2.08	28.80±5.81^a	0.27±0.04	0.48±0.07^a
5.0×10⁶	6	16.63±0.91	29.79±2.20^a	0.25±0.01	0.50±0.05^a
F值		2.055	40.88	0.2661	83.58
P值		0.100	< 0.001	0.898	< 0.001

分组	动物数（只）	mPAP（mmHg）	RVHI
对照组	6	14.76±0.81	0.26±0.01
PAH组	5	27.19±2.11^a	0.46±0.03^a
A1d组	6	24.48±4.24^a	0.49±0.06^a
A1W组	5	17.24±0.81^b	0.42±0.00^a
A2W组	6	20.27±0.49^b	0.42±0.01^a
F值		4.891	9.038
P值		0.005	< 0.001

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