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. 2019 Dec;35(12):765-771.
doi: 10.1002/kjm2.12123. Epub 2019 Sep 4.

Rhein lysinate improves motor function in rats with spinal cord injury via inhibiting p38 MAPK pathway

Jian Hao  1 , Ping Wang  1 , Dai-Ping Pei  1 , Bin Jia  1 , Qun-Sheng Hu  1
Affiliations

Rhein lysinate improves motor function in rats with spinal cord injury via inhibiting p38 MAPK pathway

Jian Hao et al. Kaohsiung J Med Sci. 2019 Dec.

Abstract

The current study aims to investigate the effect of rhein lysinate (RHL) on neuromotor function in rats with spinal cord injury (SCI) and to explore the underlying mechanism. A total of 63 adult male SD rats were randomly divided into the sham group, SCI group and RHL group (SCI-RHL group), with 21 rats in each group. Basso Beattie Bresnahan (BBB) scoring and the inclined plate test were used to evaluate the changes in motor function after SCI. Then, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) contents were quantified. Caspase-3-positive cells in spinal cord tissue were detected by immunohistochemical (IHC) staining, and protein expression was detected by Western blots. Here, our data showed that compared with the SCI group, the BBB score and inclined plate test score of the SCI-RHL group were significantly higher than those of the SCI group 7 days after the RHL intervention. After 7 days of RHL treatment, the activities of SOD and GSH-Px in the spinal cord increased significantly. At the same time, RHL reduced the MDA content in spinal cord tissue of SCI rats. Moreover, cleaved-caspase-3-positive cells and apoptotic cells were significantly lower in the SCI-RHL group than in the SCI group. More importantly, p38 mitogen-activated protein kinase (p38 MAPK) was significantly decreased in the SCI-RHL group compared with the SCI group. In summary, RHL can inhibit the activation of the p38 MAPK pathway after SCI, thereby reducing the apoptosis of spinal cord neurons and improving the neuromotor function of SCI rats.

Keywords: neuronal apoptosis; p38 mitogen-activated protein kinase; rhein lysinate; spinal cord injury.

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Conflict of interest statement

All authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Motor function was evaluated using the BBB score and inclined plate test score in each group. A, The BBB score and B, inclined plate test score in the SCI group were significantly lower than those in the sham group, while the SCI‐RHL group was significantly higher than those in the SCI group. (n = 5 for each group) *P < .05, ***P < .001 vs sham group; # P < .05 vs SCI group
Figure 2
Figure 2
RHL improved antioxidant activity in spinal cord tissues after SCI. The levels of SOD (A), GSH‐Px (B), and MDA (C) were quantified in the spinal cord tissues of the three groups. (n = 5 for each group) (D) TUNEL staining demonstrated that treatment with RHL after 7 days significantly decreased apoptosis in spinal cord tissues post SCI (scale bar represents 50 μm). (n = 5 for each group). *P < .05, ***P < .001 vs sham; # P < .05 vs SCI
Figure 3
Figure 3
RHL reduced the expression of apoptosis‐related proteins in spinal cord tissues after SCI. A, Western blot assays demonstrated that treatment with RHL after 7 days significantly decreased the expression of cleaved caspase‐3, cleaved caspase‐9 and cleaved PARP but enhanced the expression of Bcl‐2. B, IHC staining also demonstrated that c‐Caspase3‐positive cells were significantly increased in SCI rats but decreased after RHL treatment. (n = 3 for each group) *P < .05, **P < .01, ***P < .001 vs sham; #P < .05, ## P < .01 vs SCI
Figure 4
Figure 4
RHL inhibited the activation of p38 MAPK signaling after SCI for 3 days, 7 days and 14 days. (n = 3 for each group) **P < .01 vs sham; # P < .05 vs SCI
See this image and copyright information in PMC

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