Protective Effect Of Cistanche Total Glycosides Pretreatment Against Renal Ischemia Reperfusion Injury in Rats

ZHU Jun， ZHAO Xi-min

( Dept． of Surgery， Baoshan District Hospital of Integrated TCM and Western Medicine， Shanghai 201900， China)

Contact: joanna.jia@wecistanche.com / WhatsApp: 008618081934791

Cistanche deserticola has a neuroprotective effect and can prevent brain reperfusion injury

Abstract

Objective To investigate the effect of cistanche total glycosides ( CTG ) on renal ischemia-reperfusion injury in rats． Methods Thirty Sprague-Dawley rats were randomly divided into 3 groups: sham operation group， model group, and CTG group with 10 in each． Ｒenal ischemic and reperfusion injury was induced by hemorrhagic shock and resuscitation in rats of model and CTG groups． Intraperitoneal injection of 400 mg /kg CTG was given to rats in the CTG group， and injection of 3 ml normal saline was given to rats in model and sham operation groups． The serum creatinine ( Cr)， blood urea nitrogen ( BUN )， and cystatin C levels were measured， apoptosis of renal cells was detected with flow cytometry; the expression of X-linked inhibitor of apoptosis protein( XIAP) in renal tissue was determined with the ELISA method． Ｒesults Compared to the model group， blood Cr， BUN, and cystatin C in the CTG group were significantly decreased ( P ＜ 0. 01)， renal cell apoptosis was attenuated( P ＜ 0. 01)， and the expression of XIAP was increased ( P ＜ 0. 05)． Conclusion CTG can protect renal tissue against ischemia-reperfusion injury， which may be related to up-regulation of the expression of XIAP．

Keywords kidney; ischemia-reperfusion injury; cistanche total glycosides; X-linked inhibitor of apoptosis protein; apoptosis; rats

Cistanche can prevent brain reperfusion injury and resist apoptosis

Ischemia-reperfusion (I/R) injury is a common pathophysiological phenomenon of renal damage in the process of hemorrhagic shock, severe trauma, kidney transplantation, and kidney tumor surgery. Studies have shown that apoptosis is an important part of renal function damage caused by I/R injury [1]. X-linked inhibitor of apoptosis protein (X-linked inhibitor of apoptosis protein, XIAP) is one of the strongest endogenous inhibitors of apoptosis found so far [2]. There are few studies on the anti-apoptotic effect of XIAP in renal tissue after I/R injury. Cistanche total glycosides (CTG) is a phenylethanoid glycoside compound extracted from Cistanche cistanche, which has diverse biological functions. There are few studies on its renal protection after I/R injury. In this study, a rat model of hemorrhagic shock resuscitation was established, and a systemic I/R injury model was established to explore the protective effect of cistanche glycosides pretreatment on I/R injury to the kidney and explore its possible mechanism.

Result

Kidney function indexes Cr, BUN, and Cystatin C values were statistically different among the three groups (P <0.01); the experimental group was significantly higher than the sham operation group (P <0.01), indicating that the rats The kidney I/R model were successfully prepared; compared with the experimental group, the values of Cr, BUN and Cystatin C in the CTG group were significantly reduced (P <0.01). Renal cell apoptosis rate: In the sham operation group, only a small number of cells in the kidney tissue undergo apoptosis, and apoptotic cells accounted for 0.42% ± 0.08%. The experimental group had a significant increase in cell apoptosis, accounting for 18. 22% ± 5. 32 % (P＜0.01). Compared with the experimental group, the number of apoptosis in the CTG group was 12.71%±3.81% (P＜0.01). The effect of CTG on the expression of XIAP in I/R injured kidney tissue: the sham operation group only had a weaker expression of XIAP, while the experimental group had a significant increase in XIAP expression (P<0.01). Compared with the experimental group, the CTG group can significantly increase the expression of XIAP (P <0.05)

Discussion

The mechanism of ischemia-reperfusion kidney injury is very complicated. It is a pathological process that occurs through many pathways under the action of multiple factors, such as calcium ion overload, lipid peroxidation damage, cell apoptosis, and necrosis, among which caspase-dependent cell apoptosis is one of the main forms of renal tubular epithelial cell damage induced by I/R kidney injury [4]. The inhibitor of apoptosis protein (IAP) family is the only endogenous caspase inhibitor found in mammalian cells so far, which can effectively prevent the occurrence of cell apoptosis. XIAP is the strongest caspase inhibitory member of the IAP family, which can inhibit cell apoptosis caused by a variety of pathological stimuli, and protects damaged organs [5].

At present, the establishment of renal I/R injury animal models is mostly to remove one side of the kidney and clamp the other side of the renal pedicle or renal artery [6] to simulate the state of kidney transplantation. This study uses a hemorrhagic shock/resuscitation model, which is closer to the pathophysiological process of systemic ischemia-reperfusion that occurs in clinical traumatic shock. In this experiment, the blood BUN, Cr, and cystatin C levels of SD rats Significant improvement, severely impaired renal function, is an ideal animal model for studying I/R renal injury.

CTG is an important medicinal component of the traditional Chinese medicine Cistanche. Cistanche, which is warm in nature, sweet and salty, belongs to the kidney and large intestine meridian and was originally contained in the Shennong Materia Medica. "Ben Sutra": main five labors and seven injuries, nourish the five internal organs, strengthen yin, nourish essence and qi; "Materia Medica Huiyan": Cistanche, nourishing life gate, nourishing kidney qi, nourishing essence, and blood medicine. Cistanche has been used in China for two thousand years. It ranks No. 1 in strength-increasing formulas in the past and ranks No. 2 in nourishing formulas after ginseng. Studies have shown that Cistanche can improve sexual function, regulate neuroendocrine, improve immune function, and resist. Oxidize, promote material metabolism, protect ischemic myocardium and other functions. As the main medicinal ingredient of Cistanche, CTG has a multi-faceted effect. Studies in the cerebral ischemia-reperfusion model found that CTG can reduce the excitatory amino acids in the brain tissue after ischemia-reperfusion and protect the brain tissue of SD rats [7]. CTG has an antioxidant effect on mouse tissues and has a certain protective effect on acute cerebral hypoxia in mice and myocardial injury in mice [8]. CTG can significantly improve the neurobehavior of Parkinson's model mice and inhibit the decrease in the number of dopamine neurons in the substantia nigra [9]. By enhancing the activity of free radical scavenging enzymes, preventing lipid peroxidation, inhibiting the deposition of β-amyloid peptide in the brain, and inhibiting brain cell apoptosis, CTG significantly improves the learning of mice with Alzheimer's disease caused by β-amyloid peptide Memory ability [10]. This study showed that after the application of CTG pretreatment, the blood BUN, Cr, and cystatin C contents of rats decreased significantly, and the renal damage was reduced. CTG increased the apoptosis-inhibiting protein XIAP in I/R damaged kidney tissue and blocked cell apoptosis. The occurrence of death has a protective effect on the damage to the kidney.

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